The ribosome-engaged landscape of alternative splicing.
High-throughput RNA sequencing (RNA-seq) has revealed an enormous complexity of alternative splicing (AS) across diverse cell and tissue types. However, it is currently unknown to what extent repertoires of splice-variant transcripts are translated into protein products. Here, we surveyed AS events engaged by the ribosome. Notably, at least 75% of human exon-skipping events detected in transcripts with medium-to-high abundance in RNA-seq data were also detected in ribosome profiling data. Furthermore, relatively small subsets of functionally related splice variants are engaged by ribosomes at levels that do not reflect their absolute abundance, thus indicating a role for AS in modulating translational output. This mode of regulation is associated with control of the mammalian cell cycle. Our results thus suggest that a major fraction of splice variants is translated and that specific cellular functions including cell-cycle control are subject to AS-dependent modulation of translation output.
Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.|MRC Laboratory of Molecular Biology, Cambridge, UK.
Robert J
RJ
Weatheritt
Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Timothy
T
Sterne-Weiler
Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Benjamin J
BJ
Blencowe
D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D002453:Cell Cycle; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007438:Introns; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D012335:RNA, Ribosomal / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics*; D017423:Sequence Analysis, RNA
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D012335:RNA, Ribosomal