• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
FEBS Lett. Author manuscript; available in PMC Jan 21, 2011.
Published in final edited form as:
PMCID: PMC2796832
NIHMSID: NIHMS158177

Transfer RNA processing in Archaea: unusual pathways and enzymes

Abstract

Transfer RNA (tRNA) molecules are highly conserved in length, sequence and structure in order to be functional in the ribosome. However, mostly in archaea, the short genes encoding tRNAs can be found disrupted, fragmented, with permutations or with non-functional mutations of conserved nucleotides. Here, we give an overview of recently discovered tRNA maturation pathways that require intricate processing steps to finally generate the standard tRNA from these unusual tRNA genes.

Keywords: tRNA processing, trans-splicing, tRNA introns, splicing endonuclease, C-to-U editing

Introduction

Transfer RNAs (tRNAs) are small RNA molecules that transfer amino acids to a growing polypeptide chain within the ribosome. This essential role necessitates that the different tRNA species are divergent enough to allow specificity for their cognate aminoacyl-tRNA synthetase which ensures the correct pairing of amino acids and tRNAs [1]. These crucial differences between tRNA species are manifested in specific sets of recognition elements within the sequence and structure of tRNA species that together define their identity.

On the other hand, all tRNA molecules need to be similar enough to be recognized by the translation elongation factors and to fit into the tRNA binding sites of the ribosome. Thus, all canonical tRNAs have a comparable length of approximately 74–95 nucleotides (nt) and fold into a similar secondary (“cloverleaf”) and tertiary structure (“L-shape”). This is ensured by the fixed length of the tRNAs molecules’ stems and loops and by conserved nucleotides that form secondary and tertiary base interactions.

Transcription of tRNA genes generates precursor tRNAs (pre-tRNAs) that need to be processed, e.g. trimmed at both termini, and modified to produce a mature, functional tRNA molecule. Thus, the most straight-forward way to obtain functional tRNA molecules is a genome with simple short tRNA genes that allow the direct production of a precursor transcript that after cleavage of 5′ leader and 3′ trailer has the sequence of the mature tRNA. However, mainly in archaea within the last few years a surprising number of differently re-arranged and interrupted tRNA genes were discovered that often require complex processing to generate the final standard tRNA product. Here, we will give an overview of unusual tRNA processing events in archaea, and concentrate on unique tRNA gene rearrangements, and the enzymes and steps that are needed to create a continuous tRNA sequence. As this final tRNA sequence could have been directly encoded in the genome, it is necessary to analyze why these “puzzle” steps were maintained or introduced during evolution.

1. Diverse introns in tRNA genes

The notion that the sequence of a tRNA gene can contain elements which are not represented in the mature RNA transcripts was first put forth in 1977 with the discovery of introns within yeast tRNA [2,3]. It was established that nuclear tRNA genes of eukaryotes can contain one intron that is always located at a fixed position between the two nucleotides (37/38 in the standard nomenclature) following the anticodon. This required positioning allows splicing by the eukaryotic splicing endonuclease. The endonuclease recognizes the body of the mature tRNA and uses a so-called “ruler-mechanism” to measure the distance towards the cleavage site [4]. While these cleavage sites are located within unpaired regions with little sequence conservation, it became evident that the intron is an active participant in the splicing reaction by forming an important anticodon-intron base pair adjacent to the 3′ cleavage site [5].

Bacterial tRNA genes can contain a different type of introns within the anticodon region, namely the group I intron [6,7]. These self-splicing catalytic RNAs carry out both phosphodiester-cleavage and ligation reactions which remove noncoding intronic sequences and join the mature tRNA sequences [8].

The third domain of life, the Archaea, displays the most intron insertions in tRNA genes. It is estimated that approximately 15% of all archaeal tRNA genes contain introns and members of the archaeal order Thermoproteales can contain introns in about 70% of their tRNA genes [9,10]. These introns vary in size between 16 and 44 nucleotides and can be inserted at various positions and some tRNA genes even contain two or three introns (Fig. 1) [11]. Most tRNA genes with two introns and all tRNA genes with three introns are found in the genomes of Thermoproteales. Here, among the most extreme cases are the tRNA genes of Thermofilum pendens and Pyrobaculum calidifontis of which 87% include introns and half of these genes have more than one intron [10]. It is important to note that these introns display an unusual degree of conservation. For example, identical introns are located at positions 22/23 and 43/44 of the tRNAAsn (GTT) and tRNAIle (GAT) genes in T. pendens or at position 53/54 of tRNApro (TGG) and tRNAAla (TGC) genes in P. calidifontis, even though the tRNA bodies of these two species show clear differences [10]. It is tempting to speculate that this degree of conservation indicates a late acquisition of these introns as these disruptive sequences should be allowed to mutate at an equal or even faster rate than the exons containing the mature tRNA sequences.

Figure 1
Schematic overview of precursor-tRNAs that require splicing endonuclease processing

The described propagation of introns is made possible by an intron-cleavage reaction that does not follow the eukaryotic ruler mechanism and is independent of the tRNA body. The hallmark structure for archaeal introns is the Bulge-Helix-Bulge (BHB) motif; two three nucleotide bulges on opposite sides of a central 4 nucleotide helix. The independence of this motif to function as a splicing determinant is exemplified by the presence of BHB-type introns even within ribosomal RNA and messenger RNA [1214].

2. The archaeal splicing endonuclease

A BHB-motif is recognized by the archaeal splicing endonculease which cleaves the intron-exon junction within each bulge. Interestingly, this mode of splice site recognition is still functional in eukaryotic splicing endonucleases [15,16]. The allowed variance of tRNA intron position and BHB sequence and structure conservation differs among the three archaeal kingdoms and co-evolved with different archaeal splicing endonuclease families [17,18]. Most Euryarchaeota contain either homotetrameric or homodimeric enzymes that require a more conserved BHB motif than the heterotetrameric enzymes found in Crenarchaeota. Here, the relaxed BHB motifs sometimes contain only one 3 nucleotide bulge and splicing occurs even in two or four nucleotide bulges [9,19]. Also, the more frequent occurrence of multiple introns and introns at locations other than the anticodon can be linked to the emergence of this heterodimeric enzyme variant.

Crystal structures have been solved for representative enzymes from all three families [17,2022]. The crystal structure of a homodimeric splicing endonuclease bound to its substrate RNA containing a BHB motif has also been obtained (Fig. 2) [23]. These structural studies helped to reveal the structural and catalytic similarities among splicing endonucleases.

Figure 2
Crystal structure of the homodimeric splicing endonuclease from Archaeoglobus fulgidus in complex with a Bulge-Helix-Bulge RNA substrate

All tRNA splicing endonucleases form a similar four subunit quaternary structure with the subunits of the homodimeric variant being nearly twice the size of the homotetrameric enzyme. These four units display two active sites located approximately 27 Å apart from each other, which corresponds with the distance between the two cleavage sites in BHB RNA substrates. The three bulge nucleotides are flipped out of their usual stacking positions and the first bulge nucleotide is sandwiched between two conserved arginine residues. The splicing endonculease contains conserved tyrosine, histidine and a lysine residue in their catalytic triad and produces 2′,3′-cyclic phosphate and 5′-hydroxyl termini which suggests that its cleavage mechanism is highly similar to RNase A catalyzed cleavage. The tyrosine residue facilitates deprotonation of the 2′-nucleophilic oxygen, and histidine acts as the general acid donating a proton to the 5′ leaving group (for a more detailed review see [24])

Very recently, the unique acceptance of relaxed motifs of the heteromeric enzyme “was analyzed and structures from N. equitans and Pyrobaculum aerophilum “were obtained [21,22]. The catalytic subunit is inactive unless oligomerized with a second, structural subunit. A protein engineering experiment converting an inactive catalytic subunit of the heterotetrameric enzyme into a monomer of a homotetrameric splicing endonuclease restored its catalytic activity and demonstrated, that this subunit contains all of the features responsible for the broad substrate specificity [25]. Similarly, this specificity was preserved even when the structural and the catalytic subunits of the heterotetrameric variant were fused, which converted the enzyme into a homodimer [22]. A unique loop in the crenarchaeal heteromeric enzyme is suggested to play an important role in splicing activity [22] However, deletion of this loop rendered the enzyme inactive even towards canonical BHB motifs. Thus, specificity differences might be manifested in the active site of the catalytic subunit. Indeed, the active site analyzed in the in the structure of the N. equitans endonuclease contains an altered conformation of the catalytic histidine and tyrosine residues and a slightly larger catalytic pocket compared to the Archaeoglobus fulgidus enzyme [21]. It is anticipated that a co-crystal structure of the heteromeric enzyme with a relaxed BHB RNA substrate will provide further insights into the differences of this protein-RNA interaction among the three archaeal endonuclease families.

3. Split and tri-split tRNA genes

A different type of disrupted tRNA gene was discovered in 2005 in Nanoarchaeum equitans [26,27]. The tiny and compact genome of this organism contains 34 continuous tRNA genes and four tRNA genes with introns, but for 6 essential tRNA isoacceptors a tRNA gene could not easily be identified by tRNA gene scanning algorithms. Surprisingly, the tRNAs were found to be pieced together from individually expressed tRNA halves. The tRNA half genes possess their own promoter, are not required to be located in the vicinity of their matching half and can even be located on different strands. The split tRNAGlu isoacceptors presented a special case as the two 5′ tRNA halves (with anticodons CUC and UUC) are matched with only one 3′ tRNA half. Analysis of the processing pathway required to generate standard tRNA from the tRNA halves revealed a striking similarity to the processing of tRNA introns. Each 3′ tRNA half is preceded by a leader sequence that is the exact reverse complement to a sequence that is located downstream of its matching 5′ tRNA half (Fig. 1). These sequences are expected to form an up to 14 nt long helix that is thought to mediate the initial joining and folding of the tRNA halves. Structural sequences were observed at the junctions between this helix and the tRNA that strongly suggest the presence of relaxed BHB motifs [27]. The location of the split is in most cases between the bases 37 and 38, which is also the position of canonical introns. Biochemical experiments verified that the heteromeric N. equitans splicing endonuclease is able to cleave these motifs in addition to processing pre-tRNA with introns [18,19]. Thus, both splicing in cis and in trans occurs in the same organism. The generated splicing products could be ligated to form the correct mature tRNA [21].

In 2009, further instances of split tRNA genes were identified in the archaeon Caldivirga maquilingensis [28]. Again, helices are formed between the tRNA halves that mediate joining, and BHB motifs that allow the trans-splicing of these tRNAs are present. The split tRNA isoacceptors differ between N. equitans and C. maquilingensis with tRNAGlu (UUC) being the only overlap. Most surprisingly, in C. maquilingensis a more complicated event of trans-splicing was discovered that involves three tRNA fragments to be puzzled into the mature tRNAGly (UCC) and tRNAGly (CCC) (Fig. 1). Here, one 3′ half fragment is used for both of these tRNA isoacceptors and also tRNAGly (CCC) that is split into the “standard” two fragments. Two very small 12 nt tRNA fragments containing the respective anticodons are inserted between the universal 3′ tRNAGly half and the shortened 5′ tRNAGly fragment (Fig. 1). The genes for these small tRNA pieces also contain their own promoter and flanking sequences, that are able to base-pair with the extensions found in the 5′ and 3′ tRNA halves.

Where do these small tRNA fragments come from? The presence of BHB motifs and the location of the split of tRNAs (either the canonical 37/38 or the Thermoproteales-specific intron position 25/26) implies an evolutionary relationship with tRNA introns. Indeed, there is some sequence evidence for this relationship. The leader sequence of the 5′ tRNA half of N. equitans tRNALys contains 50 % identity with the intron from Pyrobaculum aerophilum tRNAArg that disrupts the tRNA gene at the same position [29]. Also, the tRNA intron of tRNAAla TGC) from Pyrobaculum islandicum shares 90% sequence identity with the leader sequences of the two 3′ tRNAAla (CGC/TGC) isoacceptor halves [28].

The limited number of known split tRNA genes does not allow us to clearly determine which tRNA disruption (introns or split tRNAs joined by intervening matching sequences) preceded the other. It has been hypothesized, that split tRNA genes represent the ancient form of tRNA gene organization [30]. On the other hand, split tRNA genes might have emerged from genome rearrangements at intron-containing tRNA genes. It should be noted, that one split tRNA gene, the 3′ tRNA half gene corresponding to both N. equitans tRNAGlu isoacceptors is located directly adjacent to a fast-evolving Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) element. Thus, insertion and excision of CRISPR elements could have been one factor in the spreading of tRNA halves.

4. Permuted tRNA genes

Yet another way to disrupt tRNA genes was discovered in 2007 in the nuclear genome of the red alga Cyanidioschyzon merolae [31]. Here, the tRNA genes are also fragmented into 5′ and 3′ tRNA halves which are, however, found inverted within a single gene. Thus, the promoters are followed by the 3′ tRNA half preceding its matching 5′ tRNA half. Surprisingly, the processing mechanism resembles splicing and trans-splicing in archaea. An intervening sequence between the two halves allows the tRNA to fold, generating a BHB-like motif at their termini (Fig. 1). This motif can then be processed by the splicing endonuclease which generates a circular intermediate. After removal of the intervening sequence (e.g. by RNase P and tRNase Z), the mature tRNA is assembled. In total, 10 tRNA genes are found permuted in C. merolae. In six of these genes, the BHB containing sequences are again inserted one nucleotide downstream of the anticodon implying an evolutionary relationship with introns. Further proof for this notion is that one permuted tRNA gene (tRNALeu (UAA)) is not only processed into a circular intermediate by splicing a BHB motif in its D-loop but also contains a BHB-motif intron in its anticodon loop. The final two permuted tRNA genes are processed at their T-loop. The occurrence of BHB motifs indicates an intriguing similarity to archaeal tRNA processing and we might soon find instances of permuted tRNA genes in archaea.

5. C-to-U editing in Methanopyrus kandleri

Sometimes smaller changes are required to change the sequence of the initial pre-tRNA transcript into the sequence of the mature tRNA. These changes include the maturation of 5′ and 3′ termini or even editing of bases within the pre-tRNA. C-to-U editing has recently been discovered to overcome the presence of a mutation that would otherwise impair the proper folding and functionality of tRNAs in Methanopyrus kandleri. Currently, this organism has the only sequenced genome in which the majority of tRNA genes (30 out of 34) contain a C at position 8 which otherwise is a highly conserved U8 that, in the mature tRNA, forms a structurally important tertiary base-pair with A14 (Fig. 3A) [32]. Initially, it was thought that M. kandleri might tolerate tRNAs with this unusual mutation, but the sequencing of mature tRNAs showed the presence of the standard U8. An enzyme was identified and characterized that specifically converts C8 to U8 [33]. This enzyme was named CDAT8 (for cytidine deaminase acting on tRNA base 8). The dimeric crystal structure of CD AT8 revealed a modular domain organization with a cytidine deaminase domain that is linked to a THUMP domain (Fig. 3B). This domain mediates RNA binding and is also found in other enzymes that act on the tertiary core of tRNA. One example is an enzyme termed Thi1, which catalyzes the thiolation of U8. The fusion of a cytidine deaminase to this THUMP domain enabled C-to-U editing activity at position 8 and therefore allowed the introduction of C8 mutations in tRNA genes. A search for sequence or structural homologs of this enzyme revealed no proteins with a similar architecture, thus classifying it as an orphan-protein so far only found in M. kandleri. This observation is in agreement with the currently unique occurrence of C8 mutations in tRNA genes. The isolated cytidine deaminase of CDAT8 was shown to belong to a unique family within the “cytidine deaminase-like” superfamily. This domain has the same core structure as those of known cytidine deaminases such as APOBEC2 [34] and APOBEC3G [35], yet is more compact.

Figure 3
C-to-U editing in Methanopyrus kandleri and CCA addition in Archaeoglobus fulgidus

It remains an intriguing question why such a mutation is beneficial to the cell, as clearly the U8, essential in the mature tRNA, could easily be encoded in the tRNA gene. This implies that a strong evolutionary pressure exists in M. kandleri that favours a C8 in the steps leading towards the mature tRNA (either the tRNA gene or tRNA-precursor without modifications or without proper folding) and that competed with the evolutionary pressure for a U8 in the final tRNA product.

6. The CCA-adding enzyme

Processing of pre-tRNAs is found in all three domains of life to guarantee the generation and quality-check of the correct 5′ and 3′ termini of tRNA molecules. An important portion of each mature tRNA is the 3′ CCA end, the three 3′ terminal bases required for the aminoacylation by aminoacyl-tRNA synthetases and for peptide-bond formation on ribosomes [36]. These CCA ends are not always encoded in the tRNA genes but a CCA-adding enzyme [ATP (CTP): tRNA nucleotidyltransferase] uses CTP and ATP as substrates to construct or repair the tRNAs’ 3′CCA end [37]. This CCA-adding enzyme is found in all three domains of life and is indispensible in organisms that contain tRNA genes that do not include the CCA sequence. The archaeal CCA-adding enzymes belong to a different class than the bacterial/eukaryotic proteins within the nucleotidyltransferase superfamily and show no homology outside of the catalytic nucleotidyltransferase domain. Both classes have similar dimensions and domain architectures with four domains termed head, neck, body, and tail (Fig. 3C). The CCA-adding enzyme has the remarkable ability to polymerize CCA onto the 3′ terminus of pre-tRNAs without a nucleic acid template. Crystal structures of the A. fulgidus enzyme with different RNA substrates indicated that the discrimination between CTP or ATP at each addition step arises from changes in the size and shape of the single nucleotide binding pocket that is progressively altered by the elongating 3′ end of the tRNA [3840]. The A. fulgidus CCA-adding enzyme is a homodimer with each monomer binding one tRNA molecule with its body and tail domains [39,40]. The 3′-terminus of the tRNA is located in the catalytic cleft formed by head and neck domains and the enzyme tail domain firmly anchors the T loop of the tRNA to ensures accurate polymerization and termination [39,40] (Fig. 3C). It is suggested that the 3′-region of the tRNA is proofread after two nucleotide additions at the AMP incorporation stage which is a prerequisite for the maintenance of fidelity for complete CCA synthesis [41].

7. The tRNAHis guanylyltransferase

A different residue that is either encoded as part of the tRNA gene or added post-transcriptionally is the unusual extra guanosine at the -1 position of the 5′ end of tRNAHis. The unique G-1:C73 base pair and the 5′-monophosphate were shown to be a major identity elements for the E.coli histidyl-tRNA synthetase [42]. Two different strategies are employed to ensure the presence of G-l and hence the recognition of tRNAHis by histidyl-tRNA synthetase. In most bacteria, the G-l residue is encoded in the tRNA gene and preserved due to an unusual RNaseP cleavage (Figure 4). Bacterial RNase P normally removes 5′ leader sequences from pre-tRNA molecules at tRNA base 1 but specifically cleaves at the -1 position only in the pre-tRNAHis [43]. Eukaryotes use a different strategy and add the crucial identity element post-transcriptionally after standard RNaseP cleavage of the precurser tRNAHis (Figure 4). This G-1 adding enzyme is termed tRNAHis-guanylyl-transferase (Thg1) and is best described in yeast [44,45]. Recently, this enzyme has also been discovered in archaea. Here, the Methanosarcinales display a puzzling scenario, as at first glance it is not clear which of the two routes is chosen, since these organisms encode a G-1 in their genomes, but also contain an open reading frame for a Thg1 homolog. Recent studies in our laboratory have shown that M. acetivorans Thg1 is expressed in vivo and is active in vitro on tRNA transcripts that lack G-1 and contain C73 [46]. Interestingly, the Methanosarcina acetivorans Thg1 contains a unique pyrrolysine residue, the rare 22nd amino acid, which is not crucial for catalytic activity [46]. This observation indicates that there is some flexibility in both the processing of tRNAHis and the biochemical role of pyrrolysine.

Figure 4
Pathways to ensure the presence of G-1 in tRNAHis

8. RNase P is missing in N. equitans

Finally, one surprising discovery was made in 2008 in N. equitans, which was shown to currently be the only known organism that can live without RNase P [47]. In archaea, RNase P, responsible for the 5′ maturation of tRNA, is a ribonucleoprotein that consists of a catalytic RNA and up to four protein subunits. Both biochemical and computational analyses did not identify any of these RNase P components or split versions in the genome of N. equitans [48]. This observation led to a number of questions as to how this organism could compensate for their absence. One clue was obtained by genome analysis that identified a strict promoter placement generating tRNAs without 5′ leader sequences and thus eliminating the need for removal of these leaders by RNase P. In addition, transcription initiation known to occur at purine residues is ensured at the start of the tRNA gene by the addition of extra purine residues at the -1 position. This includes the genes for the initiator tRNA and tRNATyr, which requires a C at position 1 as an identity element for the tyrosyl-tRNA synthetase. It was shown that RNase P cleavage with Escherichia coli RNase P would remove this extra -1 purine base. The absence of RNase P was substantiated by showing triphosphorylated 5′termini of nanoarchaeal tRNA molecules. It appears that the observed genome rearrangements allowed the absence of RNase P in N. equitans. The extremely small genome of N. equitans might indicate that the need for genome size reduction led to the loss of RNase P.

9. Conclusion

With the emergence of new genomes and new genome annotation tools, it became evident that many organisms do not follow the straight-forward way of small continuous genes encoding tRNAs. Instead, these genes can be disrupted, separated into two or three fragments or even permuted. One thing in common in all these cases is the presence of a splicing machinery that recognizes the boundaries between the exons and the disruptive sequences and is able to splice these pre-tRNAs. The heteromeric splicing endonuclease tolerates and processes relaxed BHB splicing motifs at different positions within the tRNA. While the presence of this splicing machinery ensures that the final mature tRNA is functional, the presence or necessity of these complicated tRNA gene rearrangements is puzzling. We earlier proposed that the sole function of any extra sequences within a pre-tRNAs is to disrupt tRNA genes [49], as only very few tRNA introns appear long or structured enough to have additional functions. One notable exception is the intron in the Haloferax volcanii tRNATrp that mediates the RNA-guided 2′-O methylations of C34 and U39 residues of this tRNA [50].

Why would any form of disruption of tRNA genes be beneficial to the cell? We hypothesize that the utilization of large portions of tRNA genes as attachment sites for integrative elements plays an important role. For example, archaeal viruses use tRNA genes as integration targets. These small and highly conserved RNA genes constitute a convenient target and display less tolerance for mutations compared to genes encoding proteins. The insertion and excision of integrative elements at tRNA genes might be responsible for the creation of tRNA gene disruptions that occasionally destroys the attachment site and thus provide the direct evolutionary advantage of immunity against further integration events. It remains to be seen if the occurrence of multiple disruptive elements within one tRNA gene are an adaptation to viruses that evolved to target tRNA with simple disruptions in the on-going battle between viruses and their hosts. The drastic increase in intron numbers in Thermoproteales might be explained by retrotransposition events that are responsible for the insertion of identical introns within different tRNAs [10]. Clearly, a deeper analysis of this hypothesis requires the isolation and sequencing of further archaeal intergrative elements.

Other archaeal single base processing events like the post-transcriptional correction of U8-to-C8 mutations at this structurally essential position remain to be functionally analyzed. It is plausible that these reactions provide means of regulating tRNA maturation and availability of functional tRNA molecules. It might be possible that the required C-to-U editing is a checkpoint to ensure the correct order of tRNA folding and modification including thiolation of the U8 base.

A third group of enzymes that catalyze e.g. the addition of a G-l residue in tRNAHis or also the addition 3′-terminal CCA end, ensures the integrity of tRNA termini maturation even after initial processing of the pre-tRNA transcript. In conclusion, a large number of tRNA processing pathways are present in the cell and preserve the correct sequence, folding and functionality of the final tRNA molecule even if the tRNA gene is distorted or lacks conserved tRNA features. These processing pathways can be quality-control mechanisms to ensure the presence of essential tRNA features and might also enable the cell to mutate its genome at otherwise strictly conserved regions.

Acknowledgments

We thank Dieter Jahn, Patrick O’Donoghue, Kelly Sheppard and Jing Yuan for help and encouragement. The work in the authors’ laboratory was supported by grants (to D.S.) from the National Institute of General Medical Sciences, the NSF and the Department of Energy. I.U.H. is a Postdoctoral Fellow of the Deutsche Forschungsgemeinschaft (HE5802/1-1).

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

References

1. Ibba M, Söll D. Aminoacyl-tRNA synthesis. Annu Rev Biochem. 2000;69:617–50. [PubMed]
2. Goodman HM, Olson MV, Hall BD. Nucleotide sequence of a mutant eukaryotic gene: the yeast tyrosine-inserting ochre suppressor SUP4-o. Proc Natl Acad Sci USA. 1977;74:5453–7. [PMC free article] [PubMed]
3. Valenzuela P, Venegas A, Weinberg F, Bishop R, Rutter WJ. Structure of yeast phenylalanine-tRNA genes: an intervening DNA segment within the region coding for the tRNA. Proc Natl Acad Sci USA. 1978;75:190–4. [PMC free article] [PubMed]
4. Reyes VM, Abelson J. Substrate recognition and splice site determination in yeast tRNA splicing. Cell. 1988;55:719–30. [PubMed]
5. Baldi MI, Mattoccia E, Bufardeci E, Fabbri S, Tocchini-Valentini GP. Participation of the intron in the reaction catalyzed by the Xenopus tRNA splicing endonuclease. Science. 1992;255:1404–8. [PubMed]
6. Haugen P, Simon DM, Bhattacharya D. The natural history of group I introns. Trends Genet. 2005;21:111–9. [PubMed]
7. Reinhold-Hurek B, Shub DA. Self-splicing introns in tRNA genes of widely divergent bacteria. Nature. 1992;357:173–6. [PubMed]
8. Guo F, Gooding AR, Cech TR. Structure of the Tetrahymena ribozyme: base triple sandwich and metal ion at the active site. Mol Cell. 2004;16:351–62. [PubMed]
9. Marck C, Grosjean H. Identification of BHB splicing motifs in introncontaining tRNAs from 18 archaea: evolutionary implications. RNA. 2003;9:1516–31. [PMC free article] [PubMed]
10. Sugahara J, Kikuta K, Fujishima K, Yachie N, Tomita M, Kanai A. Comprehensive analysis of archaeal tRNA genes reveals rapid increase of tRNA introns in the order thermoproteales. Mol Biol Evol. 2008;25:2709–16. [PubMed]
11. Sugahara J, Yachie N, Arakawa K, Tomita M. In silico screening of archaeal tRNA-encoding genes having multiple introns with bulge-helix-bulge splicing motifs. RNA. 2007;13:671–81. [PMC free article] [PubMed]
12. Kjems J, Garrett RA. Novel splicing mechanism for the ribosomal RNA intron in the archaebacterium Desulfurococcus mobilis. Cell. 1988;54:693–703. [PubMed]
13. Tang TH, et al. RNomics in Archaea reveals a further link between splicing of archaeal introns and rRNA processing. Nucleic Acids Res. 2002;30:921–30. [PMC free article] [PubMed]
14. Watanabe Y, Yokobori S, Inaba T, Yamagishi A, Oshima T, Kawarabayasi Y, Kikuchi H, Kita K. Introns in protein-coding genes in Archaea. FEBS Lett. 2002;510:27–30. [PubMed]
15. Di Segni G, Borghese L, Sebastiani S, Tocchini-Valentini GP. A pre-tRNA carrying intron features typical of Archaea is spliced in yeast. RNA. 2005;11:70–6. [PMC free article] [PubMed]
16. Fabbri S, Fruscoloni P, Bufardeci E, Di Nicola Negri E, Baldi MI, Attardi DG, Mattoccia E, Tocchini-Valentini GP. Conservation of substrate recognition mechanisms by tRNA splicing endonucleases. Science. 1998;280:284–6. [PubMed]
17. Li H, Trotta CR, Abelson J. Crystal structure and evolution of a transfer RNA splicing enzyme. Science. 1998;280:279–84. [PubMed]
18. Tocchini-Valentini GD, Fruscoloni P, Tocchini-Valentini GP. Coevolution of tRNA intron motifs and tRNA endonuclease architecture in Archaea. Proc Natl Acad Sci USA. 2005;102:15418–22. [PMC free article] [PubMed]
19. Randau L, Calvin K, Hall M, Yuan J, Podar M, Li H, Söll D. The heteromeric Nanoarchaeum equitans splicing endonuclease cleaves non-canonical bulge-helix-bulge motifs of joined tRNA halves. Proc Natl Acad Sci USA. 2005;120:17934–39. [PMC free article] [PubMed]
20. Li H, Abelson J. Crystal structure of a dimeric archaeal splicing endonuclease. J Mol Biol. 2000;302:639–48. [PubMed]
21. Mitchell M, Xue S, Erdman R, Randau L, Söll D, Li H. Crystal structure and assembly of the functional Nanoarchaeum equitans tRNA splicing endonuclease. Nucleic Acids Res. 2009 in press. [PMC free article] [PubMed]
22. Yoshinari S, Shiba T, Inaoka DK, Itoh T, Kurisu G, Harada S, Kita K, Watanabe Y. Functional importance of crenarchaea-specific extra-loop revealed by an X-ray structure of a heterotetrameric crenarchaeal splicing endonuclease. Nucleic Acids Res. 2009;37:4787–98. [PMC free article] [PubMed]
23. Xue S, Calvin K, Li H. RNA recognition and cleavage by a splicing endonuclease. Science. 2006;312:906–10. [PubMed]
24. Calvin K, Li H. RNA-splicing endonuclease structure and function. Cell Mol Life Sci. 2008;65:1176–85. [PubMed]
25. Calvin K, Li H. Achieving specific RNA cleavage activity by an inactive splicing endonuclease subunit through engineered oligomerization. J Mol Biol. 2007;366:642–9. [PMC free article] [PubMed]
26. Randau L, Münch R, Hohn MJ, Jahn D, Söll D. Nanoarchaeum equitans creates functional tRNAs from separate genes for their 5′- and 3′-halves. Nature. 2005;433:537–41. [PubMed]
27. Randau L, Pearson M, Söll D. The complete set of tRNA species in Nanoarchaeum equitans. FEBS Lett. 2005;579:2945–7. [PubMed]
28. Fujishima K, Sugahara J, Kikuta K, Hirano R, Sato A, Tomita M, Kanai A. Tri-split tRNA is a transfer RNA made from 3 transcripts that provides insight into the evolution of fragmented tRNAs in archaea. Proc Natl Acad Sci USA. 2009;106:2683–7. [PMC free article] [PubMed]
29. Fujishima K, Sugahara J, Tomita M, Kanai A. Sequence Evidence in the Archaeal Genomes that tRNAs Emerged Through the Combination of Ancestral Genes as 5′ and 3′ tRNA Halves. PLoS ONE. 2008;3:e1622. [PMC free article] [PubMed]
30. Di Giulio M. Formal Proof that the Split Genes of tRNAs of Nanoarchaeum equitans Are an Ancestral Character. J Mol Evol. 2009 in press. [PubMed]
31. Soma A, Onodera A, Sugahara J, Kanai A, Yachie N, Tomita M, Kawamura F, Sekine Y. Permuted tRNA genes expressed via a circular RNA intermediate in Cyanidioschyzon merolae. Science. 2007;318:450–3. [PubMed]
32. Palmer JR, Baltrus T, Reeve JN, Daniels CJ. Transfer RNA genes from the hyperthermophilic Archaeon, Methanopyrus kandleri. Biochim Biophys Acta. 1992;1132:315–8. [PubMed]
33. Randau L, Stanley BJ, Kohlway A, Mechta S, Xiong Y, Söll D. A cytidine deaminase edits C to U in transfer RNAs in Archaea. Science. 2009;324:657–9. [PMC free article] [PubMed]
34. Prochnow C, Bransteitter R, Klein MG, Goodman MF, Chen XS. The APOBEC-2 crystal structure and functional implications for the deaminase AID. Nature. 2007;445:447–51. [PubMed]
35. Chen KM, Harjes E, Gross PJ, Fahmy A, Lu Y, Shindo K, Harris RS, Matsuo H. Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature. 2008;452:116–9. [PubMed]
36. Xiong Y, Steitz TA. A story with a good ending: tRNA 3′-end maturation by CCA-adding enzymes. Curr Opin Struct Biol. 2006;16:12–7. [PubMed]
37. Weiner AM. tRNA maturation: RNA polymerization without a nucleic acid template. Curr Biol. 2004;14:R883–5. [PubMed]
38. Xiong Y, Li F, Wang J, Weiner AM, Steitz TA. Crystal structures of an archaeal class I CCA-adding enzyme and its nucleotide complexes. Mol Cell. 2003;12:1165–72. [PubMed]
39. Xiong Y, Steitz TA. Mechanism of transfer RNA maturation by CCA-adding enzyme without using an oligonucleotide template. Nature. 2004;430:640–5. [PubMed]
40. Tomita K, Ishitani R, Fukai S, Nureki O. Complete crystallographic analysis of the dynamics of CCA sequence addition. Nature. 2006;443:956–60. [PubMed]
41. Toh Y, Numata T, Watanabe K, Takeshita D, Nureki O, Tomita K. Molecular basis for maintenance of fidelity during the CCA-adding reaction by a CCA-adding enzyme. EMBO J. 2008;27:1944–52. [PMC free article] [PubMed]
42. Connolly SA, Rosen AE, Musier-Forsyth K, Francklyn CS. G- 1:C73 recognition by an arginine cluster in the active site of Escherichia coli histidyl-tRNA synthetase. Biochemistry. 2004;43:962–9. [PubMed]
43. Orellana O, Cooley L, Söll D. The additional guanylate at the 5′ terminus of Escherichia coli tRNAHis is the result of unusual processing by RNase P. Mol Cell Biol. 1986;6:525–9. [PMC free article] [PubMed]
44. Gu W, Jackman JE, Lohan AJ, Gray MW, Phizicky EM. tRNAHis maturation: an essential yeast protein catalyzes addition of a guanine nucleotide to the 5′ end of tRNAHis. Genes Dev. 2003;17:2889–901. [PMC free article] [PubMed]
45. Jackman JE, Phizicky EM. Identification of critical residues for G-1 addition and substrate recognition by tRNA(His) guanylyltransferase. Biochemistry. 2008;47:4817–25. [PubMed]
46. Heinemann IU, O’Donoghue P, Madinger C, Benner J, Randau L, Noren C, Söll D. The appearance of pyrrolysine in tRNAHis guanylyltransferase by neutral evolution. Proc Natl Acad Sci USA. 2009 submitted. [PMC free article] [PubMed]
47. Randau L, Schröder I, Söll D. Life without RNase P. Nature. 2008;453:120–3. [PubMed]
48. Li Y, Altman S. In search of RNase P RNA from microbial genomes. RNA. 2004;10:1533–40. [PMC free article] [PubMed]
49. Randau L, Söll D. Transfer RNA genes in pieces. EMBO Rep. 2008;9:623–8. [PMC free article] [PubMed]
50. Clouet d’Orval B, Bortolin ML, Gaspin C, Bachellerie JP. Box C/D RNA guides for the ribose methylation of archaeal tRNAs. The tRNATrp intron guides the formation of two ribose-methylated nucleosides in the mature tRNATrp. Nucleic Acids Res. 2001;29:4518–29. [PMC free article] [PubMed]

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...