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RNA Biol. 2015;12(11):1222-55. doi: 10.1080/15476286.2015.1038019. Epub 2015 May 13.

Genome-wide analysis of small nucleolar RNAs of Leishmania major reveals a rich repertoire of RNAs involved in modification and processing of rRNA.

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a The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute ; Bar-Ilan University ; Ramat-Gan , Israel.
b Department of Epidemiology of Microbial Diseases ; Yale University School of Public Health ; New Haven , CT USA.
c Department of Internal Medicine and Cell Biology ; Yale University Medical School ; New Haven , CT USA.
d Cell Biology ; Yale University Medical School ; New Haven , CT USA.


Trypanosomatids are protozoan parasites and the causative agent of infamous infectious diseases. These organisms regulate their gene expression mainly at the post-transcriptional level and possess characteristic RNA processing mechanisms. In this study, we analyzed the complete repertoire of Leishmania major small nucleolar (snoRNA) RNAs by performing RNA-seq analysis on RNAs that were affinity-purified using the C/D snoRNA core protein, SNU13, and the H/ACA core protein, NHP2. This study revealed a large collection of C/D and H/ACA snoRNAs, organized in gene clusters generally containing both snoRNA types. Abundant snoRNAs were identified and predicted to guide trypanosome-specific rRNA cleavages. The repertoire of snoRNAs was compared to that of the closely related Trypanosoma brucei, and 80% of both C/D and H/ACA molecules were found to have functional homologues. The comparative analyses elucidated how snoRNAs evolved to generate molecules with analogous functions in both species. Interestingly, H/ACA RNAs have great flexibility in their ability to guide modifications, and several of the RNA species can guide more than one modification, compensating for the presence of single hairpin H/ACA snoRNA in these organisms. Placing the predicted modifications on the rRNA secondary structure revealed hypermodification regions mostly in domains which are modified in other eukaryotes, in addition to trypanosome-specific modifications.


C/D; H/ACA; Leishmania; methylation; pseudouridylation; rRNA processing; snoRNA

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