Cooperative 2′-O-methylation of the wobble cytidine of human elongator tRNA(Met)(CAT) by a nucleolar and a Cajal body-specific 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. Here, we demonstrate that 2′-O-methylation of the C34 wobble cytidine of human elongator tRNA(Met)(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 tRNA(Met)(CAT) by the stress-induced endoribonuclease angiogenin, implicating box C/D guide RNPs in controlling stress-responsive production of putative regulatory tRNA fragments.