RNA ribose methylation (2′-O-methylation): Occurrence, biosynthesis and biological functions

Ayadi, Lilia; Galvanin, Adeline; Pichot, Florian; Marchand, Virginie; Motorin, Yuri

doi:10.1016/j.bbagrm.2018.11.009

Cited by 131 publications

(129 citation statements)

References 207 publications

(295 reference statements)

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“…Several studies have uncovered crucial roles for FTSJ1/TRM7 in normal and pathological conditions (reviewed in (4,5) ). While in S. cerevisiae , lack of TRM7 affected growth, FTSJ1 mutant mice showed impairment in their learning capacity as well as significantly reduced pain sensing (hypoalgesia) and altered gene expression profiles (40) .…”

Section: Introductionmentioning

confidence: 99%

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tRNA 2’-O-methylation modulates small RNA silencing and life span in Drosophila

Angelova

Dimitrova

Silva

et al. 2019

Preprint

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2'-O-methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two novel Nm methyltransferases (Nm-MTases) in Drosophila melanogaster (CG7009 and CG5220) as functional orthologs of yeast TRM7 and human FTSJ1, respectively. Genetic knockout studies together with MALDI-TOF mass spectrometry and RiboMethSeq mapping revealed that CG7009 is responsible for methylating the wobble position in tRNA Phe , tRNA Trp and tRNA Leu , while subsequently, CG5220 methylates position C32 in the same tRNAs and targets also additional tRNAs. CG7009 or CG5220 mutant animals were viable and fertile but exhibited various phenotypes such as life span reduction, small RNA pathways dysfunction and increased sensitivity to RNA virus infections. Our results provide the first detailed characterization of two TRM7 family members in Drosophila and uncover a molecular link between enzymes catalysing Nm at specific tRNAs and small RNA-induced gene silencing pathways.

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Section: Introductionmentioning

confidence: 99%

“…2'-O-methylation (Nm) is a common RNA modification. The addition of a methyl group to the 2' hydroxyl of the ribose moiety of a nucleoside creates Nm (reviewed in (4,5) ). Nm can occur at any nucleotide explaining the abundant nature of this modification.…”

Section: Introductionmentioning

confidence: 99%

tRNA 2’-O-methylation modulates small RNA silencing and life span in Drosophila

Angelova

Dimitrova

Silva

et al. 2019

Preprint

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“…Taken together, these examples demonstrate the diversity of both snoRNA targets ( Figure 4F) and of their functional impact through their 2 0 -O-methylation capacity. Together with a recent report of the detection of hundreds of 2 0 -O-methylation sites in mRNAs in HeLa and HEK cells [52], and our increasing understanding of the role of this modification, including in RNA stability, splicing and translation (as reviewed in [53]), these studies raise questions about the possibility of widespread involvement of snoRNAs in these regulatory processes.…”

Section: Chemical Modification Of Non-canonical Rnamentioning

confidence: 98%

Small nucleolar RNAs: continuing identification of novel members and increasing diversity of their molecular mechanisms of action

Bergeron

Fafard-Couture

Scott

2020

Biochemical Society Transactions

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Identified five decades ago amongst the most abundant cellular RNAs, small nucleolar RNAs (snoRNAs) were initially described as serving as guides for the methylation and pseudouridylation of ribosomal RNA through direct base pairing. In recent years, however, increasingly powerful high-throughput genomic approaches and strategies have led to the discovery of many new members of the family and surprising diversity in snoRNA functionality and mechanisms of action. SnoRNAs are now known to target RNAs of many biotypes for a wider range of modifications, interact with diverse binding partners, compete with other binders for functional interactions, recruit diverse players to targets and affect protein function and accessibility through direct interaction. This minireview presents the continuing characterization of the snoRNome through the identification of new snoRNA members and the discovery of their mechanisms of action, revealing a highly versatile noncoding family playing central regulatory roles and connecting the main cellular processes.

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“…Recently, it was postulated that rRNA modifications may provide an important source of ribosome heterogeneity, and tune ribosome function in response to various signals [76][77][78][79][80][81]. These modifications, which may be fractional at certain positions, stabilize the secondary and tertiary structure of the rRNA scaffold, thereby modulating the efficiency and accuracy of protein translation.…”

Section: Changes In Pseudouridine Levels At Specific Rrna Sitesmentioning

confidence: 99%

Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

Atari

Rajan

Chikne

et al. 2020

Preprint

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The nucleolus is a sub-nuclear compartment whose primary function is the biogenesis of ribosomal subunits. Certain viral infections affect the morphology and composition of the nucleolar compartment and influence ribosomal RNA (rRNA) transcription and maturation. However, no description of nucleolar morphology and function during infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is available to date. Using immunofluorescence microscopy, we documented extensive destruction of the nuclear and nucleolar architecture during lytic reactivation of KSHV. This was manifested by redistribution of key nucleolar proteins, including the rRNA transcription factor, UBF, the essential pre-rRNA processing factor Fibrillarin, and the nucleolar multifunctional phosphoproteins Nucleophosmin (NPM1) and Nucleolin. Distinct delocalization patterns were evident; certain nucleolar proteins remained together whereas others dissociated, implying that nucleolar proteins undergo nonrandom programmed dispersion. Of note, neither Fibrillarin nor UBF colocalized with promyelocytic leukemia (PML) nuclear bodies or with the viral protein LANA-1, and their redistribution was not dependent on viral DNA replication or late viral gene expression. No significant changes in pre-rRNA levels and no accumulation of pre-rRNA intermediates were found by RT-qPCR and Northern blot analysis, respectively. Furthermore, fluorescent in situ hybridization (FISH), combined with immunofluorescence, revealed an overlap between Fibrillarin and internal transcribed spacer 1 (ITS1), which represents the primary product of the pre-rRNA, suggesting that the processing of rRNA proceeds during lytic reactivation. Finally, small changes in the levels of pseudouridylation were documented across the rRNA. Taken together, our results suggest that rRNA transcription and processing persist during lytic reactivation of KSHV, yet they may become uncoupled. Whether the observed nucleolar alterations favor productive infection or signify cellular anti-viral responses remains to be determined. Author SummaryWe describe the extensive destruction of the nuclear and nucleolar architecture during lytic reactivation of KSHV. Distinct delocalization patterns are illustrated: certain nucleolar proteins remained associated with each other whereas others dissociated, implying that nucleolar proteins undergo nonrandom , 3 programmed dispersion. Of note, no significant changes in pre-rRNA levels and no accumulation of pre-rRNA intermediates were found, suggesting that pre-RNA transcription and processing continue and could be uncoupled during lytic reactivation. Small changes in the levels of pseudouridylation were documented across the rRNA. Previous studies showed that the different forms of KSHV infection are controlled through cellular and viral functions, which reprogram host epigenetic, transcriptomic, posttranscriptomic and proteomic landscapes. The ability of KSHV to affect the nucleolus and rRNA modifications constitutes a novel interaction network between viral and cellula...

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RNA ribose methylation (2′-O-methylation): Occurrence, biosynthesis and biological functions

Cited by 131 publications

References 207 publications

tRNA 2’-O-methylation modulates small RNA silencing and life span in Drosophila

tRNA 2’-O-methylation modulates small RNA silencing and life span in Drosophila

Small nucleolar RNAs: continuing identification of novel members and increasing diversity of their molecular mechanisms of action

Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

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