RNA-guided Nucleotide Modification of Ribosomal and Other RNAs

Abstract

ribonucleoprotein ribosomal RNA ribose-methylated nucleotide pseudouridine small nucleolar RNA small nucleolar ribonucleoprotein complex small nuclear RNA snoRNA-like RNA/RNP Cajal body nucleolar body small Cajal body RNA/RNP RNA polymerase II nucleotide(s) spliced leader One of the exciting frontiers in the field of RNA editing is the phenomenon of RNA-guided nucleotide modification. In this type of editing, a nucleotide in a precursor RNA is converted to another form by an RNA-protein complex (RNP)1 (1Kiss T. EMBO J. 2001; 20: 3617-3622Crossref PubMed Scopus (354) Google Scholar). The RNPs that mediate these reactions include a guide RNA that provides site specificity through base pairing with the substrate and a set of proteins, one of which catalyzes the modification reaction. The phenomenon was first discovered in the modification of ribosomal RNA (rRNA) in the nucleolus of eukaryotic cells (Fig. 1). Two common alterations are relevant, formation of 2′-O-methylated nucleosides (Nm; the guided mechanism was reported in 1996) and conversion of uridine to pseudouridine (Ψ; the guided process was reported in 1997) (2Kiss-Laszlo Z. Henry Y. Bachellerie J.P. Caizergues-Ferrer M. Kiss T. Cell. 1996; 85: 1077-1088Abstract Full Text Full Text PDF PubMed Scopus (662) Google Scholar, 3Ni J. Tien A.L. Fournier M.J. Cell. 1997; 89: 565-573Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar, 4Ganot P. Bortolin M.L. Kiss T. Cell. 1997; 89: 799-809Abstract Full Text Full Text PDF PubMed Scopus (494) Google Scholar). These modifications are mediated by two large, heterogeneous populations of RNPs that are modification type-specific and site-specific. The RNPs contain a small nucleolar RNA (snoRNA) and several associated proteins, and the snoRNA-protein complexes are called snoRNPs (“snorps”). The snoRNA provides the guide function, and an integral snoRNP protein catalyzes the modification reaction. When discovered, this type of reaction scheme was not only novel but in sharp contrast to the rRNA modification schemes used by Eubacteria, where the synthesis of Nm and Ψ is mediated (thus far) by protein enzymes that do not include an RNA co-factor (5Ofengand J. Rudd K. Garrett R.A. Douthwaite S.R. Liljas A. Matheson A.T. Moore P.B. Noller H.F. The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions. ASM Press, Washington, D. C.2000: 175-189Google Scholar). Guided modification was subsequently discovered to apply to the U6 snRNA (small nuclear RNA in vertebrates and Caenorhabditis elegans) and likely to mRNA (mammals, trypanosomes) (6Tycowski K.T. You Z.H. Graham P.J. Steitz J.A. Mol. Cell. 1998; 2: 629-638Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar, 7Ganot P. Jady B.E. Bortolin M.L. Darzacq X. Kiss T. Mol. Cell. Biol. 1999; 19: 6906-6917Crossref PubMed Scopus (131) Google Scholar, 8Cavaille J. Buiting K. Kiefmann M. Lalande M. Brannan C.I. Horsthemke B. Bachellerie J.P. Brosius J. Huttenhofer A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 14311-14316Crossref PubMed Scopus (471) Google Scholar, 9Liang X.H., Xu, Y.X. Michaeli S. RNA. 2002; 8: 237-246Crossref PubMed Scopus (56) Google Scholar). Strikingly, from an evolutionary perspective, the new paradigm was also discovered (in 2000) to apply to Archaeal organisms where substrates include tRNA as well as rRNA (10Dennis P.P. Omer A. Lowe T. Mol. Microbiol. 2001; 40: 509-519Crossref PubMed Scopus (112) Google Scholar). Recent advances have revealed guided modification to be more complex and widespread and are almost certainly a harbinger of exciting new developments to come. Key developments include: 1) identification of new guide RNAs that reside in mammalian Cajal bodies (these RNAs are specific for the four snRNAs transcribed by RNA polymerase II (pol II), which are thought to undergo maturation and possibly RNP assembly at this location (11Darzacq X. Jady B.E. Verheggen C. Kiss A.M. Bertrand E. Kiss T. EMBO J. 2002; 21: 2746-2756Crossref PubMed Scopus (371) Google Scholar)); 2) evidence that the trypanosome trans-spliced leader is a substrate for guided modification (9Liang X.H., Xu, Y.X. Michaeli S. RNA. 2002; 8: 237-246Crossref PubMed Scopus (56) Google Scholar); and 3) successful development of the first cell-free Nm modification system, using recombinant archaeal components (12Omer A.D. Ziesche S. Ebhardt H. Dennis P.P. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 5289-5294Crossref PubMed Scopus (160) Google Scholar). Taken together, these findings argue that additional modifying RNPs and substrates subjected to RNA-guided modification will be discovered. In this minireview we describe the present state of knowledge about the various RNP-modifying complexes, the processes they mediate, where in the cell these reactions occur, and the range of substrates. Because of limited space the reader is also referred to other recent reviews (1Kiss T. EMBO J. 2001; 20: 3617-3622Crossref PubMed Scopus (354) Google Scholar, 13We