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EMBO J. Jan 15, 1998; 17(2): 590–597.
PMCID: PMC1170408

An actively retrotransposing, novel subfamily of mouse L1 elements.

Abstract

Retrotransposition of LINEs and other retroelements increases repetition in mammalian genomes and can cause deleterious mutations. Recent insertions of two full-length L1s, L1spa and L1Orl, caused the disease phenotypes of the spastic and Orleans reeler mice respectively. Here we show that these two recently retrotransposed L1s are nearly identical in sequence, have two open reading frames and belong to a novel subfamily related to the ancient F subfamily. We have named this new subfamily TF (for transposable) and show that many full-length members of this family are present in the mouse genome. The TF 5' untranslated region has promoter activity, and TF-type RNA is abundant in cytoplasmic ribonucleoprotein particles, which are likely intermediates in retrotransposition. Both L1spa and L1Orl have reverse transcriptase activity in a yeast-based assay and retrotranspose at high frequency in cultured cells. Together, our data indicate that the TF subfamily of L1s contains a major class of mobile elements that is expanding in the mouse genome.

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Selected References

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  • Adey NB, Tollefsbol TO, Sparks AB, Edgell MH, Hutchison CA., 3rd Molecular resurrection of an extinct ancestral promoter for mouse L1. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1569–1573. [PMC free article] [PubMed]
  • Boeke JD. LINEs and Alus--the polyA connection. Nat Genet. 1997 May;16(1):6–7. [PubMed]
  • Burton FH, Loeb DD, Voliva CF, Martin SL, Edgell MH, Hutchison CA., 3rd Conservation throughout mammalia and extensive protein-encoding capacity of the highly repeated DNA long interspersed sequence one. J Mol Biol. 1986 Jan 20;187(2):291–304. [PubMed]
  • Derr LK, Strathern JN, Garfinkel DJ. RNA-mediated recombination in S. cerevisiae. Cell. 1991 Oct 18;67(2):355–364. [PubMed]
  • Dombroski BA, Mathias SL, Nanthakumar E, Scott AF, Kazazian HH., Jr Isolation of an active human transposable element. Science. 1991 Dec 20;254(5039):1805–1808. [PubMed]
  • Dombroski BA, Feng Q, Mathias SL, Sassaman DM, Scott AF, Kazazian HH, Jr, Boeke JD. An in vivo assay for the reverse transcriptase of human retrotransposon L1 in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Jul;14(7):4485–4492. [PMC free article] [PubMed]
  • Fanning TG, Singer MF. LINE-1: a mammalian transposable element. Biochim Biophys Acta. 1987 Dec 8;910(3):203–212. [PubMed]
  • Feng Q, Moran JV, Kazazian HH, Jr, Boeke JD. Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell. 1996 Nov 29;87(5):905–916. [PubMed]
  • Hohjoh H, Singer MF. Cytoplasmic ribonucleoprotein complexes containing human LINE-1 protein and RNA. EMBO J. 1996 Feb 1;15(3):630–639. [PMC free article] [PubMed]
  • Hohjoh H, Singer MF. Sequence-specific single-strand RNA binding protein encoded by the human LINE-1 retrotransposon. EMBO J. 1997 Oct 1;16(19):6034–6043. [PMC free article] [PubMed]
  • Holmes SE, Dombroski BA, Krebs CM, Boehm CD, Kazazian HH., Jr A new retrotransposable human L1 element from the LRE2 locus on chromosome 1q produces a chimaeric insertion. Nat Genet. 1994 Jun;7(2):143–148. [PubMed]
  • Kazazian HH, Jr, Wong C, Youssoufian H, Scott AF, Phillips DG, Antonarakis SE. Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature. 1988 Mar 10;332(6160):164–166. [PubMed]
  • Kingsmore SF, Giros B, Suh D, Bieniarz M, Caron MG, Seldin MF. Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet. 1994 Jun;7(2):136–141. [PubMed]
  • Kohrman DC, Harris JB, Meisler MH. Mutation detection in the med and medJ alleles of the sodium channel Scn8a. Unusual splicing due to a minor class AT-AC intron. J Biol Chem. 1996 Jul 19;271(29):17576–17581. [PubMed]
  • Kolosha VO, Martin SL. Polymorphic sequences encoding the first open reading frame protein from LINE-1 ribonucleoprotein particles. J Biol Chem. 1995 Feb 10;270(6):2868–2873. [PubMed]
  • Kolosha VO, Martin SL. In vitro properties of the first ORF protein from mouse LINE-1 support its role in ribonucleoprotein particle formation during retrotransposition. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10155–10160. [PMC free article] [PubMed]
  • Kunkel TA, Bebenek K, McClary J. Efficient site-directed mutagenesis using uracil-containing DNA. Methods Enzymol. 1991;204:125–139. [PubMed]
  • Loeb DD, Padgett RW, Hardies SC, Shehee WR, Comer MB, Edgell MH, Hutchison CA., 3rd The sequence of a large L1Md element reveals a tandemly repeated 5' end and several features found in retrotransposons. Mol Cell Biol. 1986 Jan;6(1):168–182. [PMC free article] [PubMed]
  • Martin SL. Ribonucleoprotein particles with LINE-1 RNA in mouse embryonal carcinoma cells. Mol Cell Biol. 1991 Sep;11(9):4804–4807. [PMC free article] [PubMed]
  • Mathias SL, Scott AF, Kazazian HH, Jr, Boeke JD, Gabriel A. Reverse transcriptase encoded by a human transposable element. Science. 1991 Dec 20;254(5039):1808–1810. [PubMed]
  • Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler KW, Vogelstein B, Nakamura Y. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res. 1992 Feb 1;52(3):643–645. [PubMed]
  • Moran JV, Holmes SE, Naas TP, DeBerardinis RJ, Boeke JD, Kazazian HH., Jr High frequency retrotransposition in cultured mammalian cells. Cell. 1996 Nov 29;87(5):917–927. [PubMed]
  • Morse B, Rotherg PG, South VJ, Spandorfer JM, Astrin SM. Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma. Nature. 1988 May 5;333(6168):87–90. [PubMed]
  • Mülhardt C, Fischer M, Gass P, Simon-Chazottes D, Guénet JL, Kuhse J, Betz H, Becker CM. The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element. Neuron. 1994 Oct;13(4):1003–1015. [PubMed]
  • Narita N, Nishio H, Kitoh Y, Ishikawa Y, Ishikawa Y, Minami R, Nakamura H, Matsuo M. Insertion of a 5' truncated L1 element into the 3' end of exon 44 of the dystrophin gene resulted in skipping of the exon during splicing in a case of Duchenne muscular dystrophy. J Clin Invest. 1993 May;91(5):1862–1867. [PMC free article] [PubMed]
  • Padgett RW, Hutchison CA, 3rd, Edgell MH. The F-type 5' motif of mouse L1 elements: a major class of L1 termini similar to the A-type in organization but unrelated in sequence. Nucleic Acids Res. 1988 Jan 25;16(2):739–749. [PMC free article] [PubMed]
  • Perou CM, Pryor RJ, Naas TP, Kaplan J. The bg allele mutation is due to a LINE1 element retrotransposition. Genomics. 1997 Jun 1;42(2):366–368. [PubMed]
  • Sassaman DM, Dombroski BA, Moran JV, Kimberland ML, Naas TP, DeBerardinis RJ, Gabriel A, Swergold GD, Kazazian HH., Jr Many human L1 elements are capable of retrotransposition. Nat Genet. 1997 May;16(1):37–43. [PubMed]
  • Schichman SA, Severynse DM, Edgell MH, Hutchison CA., 3rd Strand-specific LINE-1 transcription in mouse F9 cells originates from the youngest phylogenetic subgroup of LINE-1 elements. J Mol Biol. 1992 Apr 5;224(3):559–574. [PubMed]
  • Schichman SA, Adey NB, Edgell MH, Hutchison CA., 3rd L1 A-monomer tandem arrays have expanded during the course of mouse L1 evolution. Mol Biol Evol. 1993 May;10(3):552–570. [PubMed]
  • Severynse DM, Hutchison CA, 3rd, Edgell MH. Identification of transcriptional regulatory activity within the 5' A-type monomer sequence of the mouse LINE-1 retroposon. Mamm Genome. 1992;2(1):41–50. [PubMed]
  • Shehee WR, Chao SF, Loeb DD, Comer MB, Hutchison CA, 3rd, Edgell MH. Determination of a functional ancestral sequence and definition of the 5' end of A-type mouse L1 elements. J Mol Biol. 1987 Aug 20;196(4):757–767. [PubMed]
  • Skowronski J, Fanning TG, Singer MF. Unit-length line-1 transcripts in human teratocarcinoma cells. Mol Cell Biol. 1988 Apr;8(4):1385–1397. [PMC free article] [PubMed]
  • Takahara T, Ohsumi T, Kuromitsu J, Shibata K, Sasaki N, Okazaki Y, Shibata H, Sato S, Yoshiki A, Kusakabe M, et al. Dysfunction of the Orleans reeler gene arising from exon skipping due to transposition of a full-length copy of an active L1 sequence into the skipped exon. Hum Mol Genet. 1996 Jul;5(7):989–993. [PubMed]
  • Voliva CF, Jahn CL, Comer MB, Hutchison CA, 3rd, Edgell MH. The L1Md long interspersed repeat family in the mouse: almost all examples are truncated at one end. Nucleic Acids Res. 1983 Dec 20;11(24):8847–8859. [PMC free article] [PubMed]

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