Nature Structural & Molecular Biology 13, 482 - 490 (2006)
Published online: 7 May 2006; | doi:10.1038/nsmb1093
Exon ligation is proofread by the DExD/H-box ATPase Prp22pRabiah M Mayas1, Hiroshi Maita2, 3
& Jonathan P Staley21
Department of Biochemistry and Molecular Biology, The University of Chicago, Cummings Life Science Center 817, 920 E. 58th Street, Chicago, Illinois 60637, USA. 2
Department of Molecular Genetics and Cell Biology, The University of Chicago, Cummings Life Science Center 817, 920 E. 58th Street, Chicago, Illinois 60637, USA. 3
Present address: Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
Correspondence should be addressed to Jonathan P Staley jstaley@uchicago.edu To produce messenger RNA, the spliceosome excises introns from precursor (pre)-mRNA and splices the flanking exons. To establish fidelity, the spliceosome discriminates against aberrant introns, but current understanding of such fidelity mechanisms is limited. Here we show that an ATP-dependent activity represses formation of mRNA from aberrant intermediates having mutations in any of the intronic consensus sequences. This proofreading activity is disabled by mutations that impair the ATPase or RNA unwindase activity of Prp22p, a conserved spliceosomal DExD/H-box ATPase. Further, cold-sensitive prp22 mutants permit aberrant mRNA formation from a mutated 3' splice-site intermediate in vivo. We conclude that Prp22p generally represses splicing of aberrant intermediates, in addition to its known ATP-dependent role in promoting release of genuine mRNA. This dual function for Prp22p validates a general model in which fidelity can be enhanced by a DExD/H-box ATPase.
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