title: Genome-wide analysis of small nucleolar RNAs of Leishmania major reveals a rich repertoire of RNAs involved in modification and processing of rRNA.
abstract: 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.
authors.affiliation: a The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute ; Bar-Ilan University ; Ramat-Gan , Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Eliaz
authors.affiliation: a The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute ; Bar-Ilan University ; Ramat-Gan , Israel.
authors.forename: Tirza
authors.initials: T
authors.lastname: Doniger
authors.affiliation: a The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute ; Bar-Ilan University ; Ramat-Gan , Israel.
authors.forename: Itai Dov
authors.initials: ID
authors.lastname: Tkacz
authors.affiliation: a The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute ; Bar-Ilan University ; Ramat-Gan , Israel.
authors.forename: Viplov Kumar
authors.initials: VK
authors.lastname: Biswas
authors.affiliation: a The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute ; Bar-Ilan University ; Ramat-Gan , Israel.
authors.forename: Sachin Kumar
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: b Department of Epidemiology of Microbial Diseases ; Yale University School of Public Health ; New Haven , CT USA.
authors.forename: Nikolay G
authors.initials: NG
authors.lastname: Kolev
authors.affiliation: a The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute ; Bar-Ilan University ; Ramat-Gan , Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Unger
authors.affiliation: 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.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ullu
authors.affiliation: b Department of Epidemiology of Microbial Diseases ; Yale University School of Public Health ; New Haven , CT USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Tschudi
authors.affiliation: a The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute ; Bar-Ilan University ; Ramat-Gan , Israel.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Michaeli
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D015723:Gene Library; D018503:Genome, Protozoan; D055106:Genome-Wide Association Study; D018320:Leishmania major / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009690:Nucleic Acid Conformation; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D014345:Trypanosoma / Q000235:genetics / Q000378:metabolism
chemical_list: D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; D017411:Ribonucleoproteins, Small Nuclear
keywords: C/D; H/ACA; Leishmania; methylation; pseudouridylation; rRNA processing; snoRNA