Abstract
Site-specific 2'-O-ribose methylation of mammalian rRNAs and RNA polymerase II-synthesized spliceosomal small nuclear RNAs (snRNAs) is mediated by small nucleolar and small Cajal body (CB)-specific box C/D ribonucleoprotein particles (RNPs) in the nucleolus and the nucleoplasmic CBs, respectively. Here, we demonstrate that 2'-O-methylation of the C34 wobble cytidine of human elongator tRNAMet(CAT) is achieved by collaboration of a nucleolar and a CB-specific box C/D RNP carrying the SNORD97 and SCARNA97 box C/D 2'-O-methylation guide RNAs. Methylation of C34 prevents site-specific cleavage of tRNAMet(CAT) by the stress-induced endoribonuclease angiogenin, implicating box C/D guide RNPs in controlling stress-responsive production of putative regulatory tRNA fragments.
Highlights
Posttranscriptional modification of selected ribonucleotides is an important step of the biogenesis of cellular RNAs (Grosjean 2005; Boccaletto et al 2018)
We show that 2′-O-methylation of C34 protects tRNAMet(CAT) from endonucleolytic cleavage by stressinduced angiogenin
SNORD133, has been detected among RNAs coimmunopurified with the Cajal body (CB) proteins WDR79 and coilin, suggesting that it may accumulate in the CB (Jády et al 2012; Machyna et al 2014)
Summary
Cooperative 2′-O-methylation of the wobble cytidine of human elongator tRNAMet(CAT) by a nucleolar and a Cajal bodyspecific box C/D RNP. Site-specific 2′-O-ribose methylation of mammalian rRNAs and RNA polymerase II-synthesized spliceosomal small nuclear RNAs (snRNAs) is mediated by small nucleolar and small Cajal body (CB)-specific box C/D ribonucleoprotein particles (RNPs) in the nucleolus and the nucleoplasmic CBs, respectively. We demonstrate that 2′-O-methylation of the C34 wobble cytidine of human elongator tRNAMet(CAT) is achieved by collaboration of a nucleolar and a CB-specific box C/D RNP carrying the SNORD97 and SCARNA97 box C/D 2′-Omethylation guide RNAs. Methylation of C34 prevents site-specific cleavage of tRNAMet(CAT) by the stressinduced endoribonuclease angiogenin, implicating box C/D guide RNPs in controlling stress-responsive production of putative regulatory tRNA fragments. The most common site-specific RNA modification reactions (namely, 2′-O-ribose methylation of the four ribonucleotides and conversion of uridines into pseudouridine) are frequently catalyzed by evolutionarily conserved box C/D 2′-O-methylation and box H/ACA pseudouridylation and guide ribonucleoprotein particles (RNPs) (Watkins and Bohnsack 2012). GENES & DEVELOPMENT 33:741–746 Published by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/19; www.genesdev.org
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