Translational control of intron splicing in eukaryotes.

Abstract

Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poorly understood. In most organisms, short introns recognized by the intron definition mechanism cannot be efficiently predicted solely on the basis of sequence motifs. In multicellular eukaryotes, long introns are recognized through exon definition and most genes produce multiple mRNA variants through alternative splicing. The nonsense-mediated mRNA decay (NMD) pathway may further shape the observed sets of variants by selectively degrading those containing premature termination codons, which are frequently produced in mammals. Here we show that the tiny introns of the ciliate Paramecium tetraurelia are under strong selective pressure to cause premature termination of mRNA translation in the event of intron retention, and that the same bias is observed among the short introns of plants, fungi and animals. By knocking down the two P. tetraurelia genes encoding UPF1, a protein that is crucial in NMD, we show that the intrinsic efficiency of splicing varies widely among introns and that NMD activity can significantly reduce the fraction of unspliced mRNAs. The results suggest that, independently of alternative splicing, species with large intron numbers universally rely on NMD to compensate for suboptimal splicing efficiency and accuracy.

DOI: 10.1038/nature06495

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@article{Jaillon2008TranslationalCO, title={Translational control of intron splicing in eukaryotes.}, author={Olivier Jaillon and Khaled Bouhouche and Jean-Francois Gout and Jean-Marc Aury and Benjamin Noel and Baptiste Saudemont and Mariusz Nowacki and Vincent Bouchot Serrano and Betina M. Porcel and B{\'e}atrice S{\'e}gurens and Anne Le Mou{\"{e}l and Gersende Lep{\`e}re and Vincent Sch{\"a}chter and Mireille B{\'e}termier and Jean Cohen and Patrick Wincker and Linda Sperling and Laurent Duret and Eric T. Meyer}, journal={Nature}, year={2008}, volume={451 7176}, pages={359-62} }