UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Widespread exon skipping triggers degradation by nuclear RNA surveillance in fission yeast

Bitton, DA; Atkinson, SR; Rallis, C; Smith, GC; Ellis, DA; Chen, Y; Malecki, M; ... Bahler, J; + view all (2015) Widespread exon skipping triggers degradation by nuclear RNA surveillance in fission yeast. Genome Research , 25 (6) pp. 884-896. 10.1101/gr.185371.114. Green open access

[thumbnail of Bahler_Genome%20Res.-2015-Bitton-884-96.pdf]
Preview
Text
Bahler_Genome%20Res.-2015-Bitton-884-96.pdf

Download (816kB) | Preview

Abstract

Exon-skipping is considered a principal mechanism by which eukaryotic cells expand their transcriptome and proteome repertoires, creating different splice variants with distinct cellular functions. Here we analyze RNA-seq data from 116 transcriptomes in fission yeast (Schizosaccharomyces pombe), covering multiple physiological conditions as well as transcriptional and RNA processing mutants. We applied brute-force algorithms to detect all possible exon-skipping events, which were widespread but rare compared to normal splicing events. Exon-skipping events increased in cells deficient for the nuclear exosome or the 5'-3' exonuclease Dhp1, and also at late stages of meiotic differentiation when nuclear-exosome transcripts decreased. The pervasive exon-skipping transcripts were stochastic, did not increase in specific physiological conditions, and were mostly present at below 1 copy per cell, even in the absence of nuclear RNA surveillance and late during meiosis. These exon-skipping transcripts are therefore unlikely to be functional and may reflect splicing errors that are actively removed by nuclear RNA surveillance. The average splicing rate by exon-skipping was ~0.24% in wild-type and ~1.75% in nuclear exonuclease mutants. We also detected ~250 circular RNAs derived from single or multiple exons. These circular RNAs were rare and stochastic, although a few became stabilized during quiescence and in splicing mutants. Using an exhaustive search algorithm, we also uncovered thousands of previously unknown splice sites, indicating pervasive splicing, yet most of these splicing variants were cryptic and increased in nuclear degradation mutants. This study highlights widespread, but low frequency alternative or aberrant splicing events which are targeted by nuclear RNA surveillance.

Type: Article
Title: Widespread exon skipping triggers degradation by nuclear RNA surveillance in fission yeast
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/gr.185371.114
Publisher version: http://dx.doi.org/10.1101/gr.185371.114
Language: English
Additional information: © 2015 Bitton et al.; Published by Cold Spring Harbor Laboratory Press. This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
Keywords: Alternative splicing, RNA processing, S. pombe, circular RNA, exosome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1466914
Downloads since deposit
58Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item