title: 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.
authors.affiliation: Genoscope (CEA), 2 rue Gaston Crémieux CP5706, 91057 Evry, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Jaillon
authors.forename: Khaled
authors.initials: K
authors.lastname: Bouhouche
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gout
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Aury
authors.forename: Benjamin
authors.initials: B
authors.lastname: Noel
authors.forename: Baptiste
authors.initials: B
authors.lastname: Saudemont
authors.forename: Mariusz
authors.initials: M
authors.lastname: Nowacki
authors.forename: Vincent
authors.initials: V
authors.lastname: Serrano
authors.forename: Betina M
authors.initials: BM
authors.lastname: Porcel
authors.forename: Béatrice
authors.initials: B
authors.lastname: Ségurens
authors.forename: Anne
authors.initials: A
authors.lastname: Le Mouël
authors.forename: Gersende
authors.initials: G
authors.lastname: Lepère
authors.forename: Vincent
authors.initials: V
authors.lastname: Schächter
authors.forename: Mireille
authors.initials: M
authors.lastname: Bétermier
authors.forename: Jean
authors.initials: J
authors.lastname: Cohen
authors.forename: Patrick
authors.initials: P
authors.lastname: Wincker
authors.forename: Linda
authors.initials: L
authors.lastname: Sperling
authors.forename: Laurent
authors.initials: L
authors.lastname: Duret
authors.forename: Eric
authors.initials: E
authors.lastname: Meyer
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D018388:Codon, Terminator / Q000235:genetics; D019295:Computational Biology; D005057:Eukaryotic Cells / Q000378:metabolism*; D020224:Expressed Sequence Tags; D017125:Genes, Protozoan / Q000235:genetics; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D010247:Paramecium / Q000235:genetics*; D014176:Protein Biosynthesis; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020871:RNA Stability; D016053:RNA, Protozoan / Q000235:genetics / Q000378:metabolism
chemical_list: D018388:Codon, Terminator; D015800:Protozoan Proteins; D016053:RNA, Protozoan