Long noncoding RNA repertoire and targeting by nuclear exosome, cytoplasmic exonuclease, and RNAi in fission yeast
- Sophie R. Atkinson1,7,
- Samuel Marguerat1,2,3,7,
- Danny A. Bitton1,7,
- Maria Rodríguez-López1,
- Charalampos Rallis1,8,
- Jean-François Lemay4,
- Cristina Cotobal1,
- Michal Malecki1,
- Pawel Smialowski5,9,
- Juan Mata6,
- Philipp Korber5,
- François Bachand4 and
- Jürg Bähler1
- 1Research Department of Genetics, Evolution and Environment and UCL Genetics Institute, University College London, London WC1E 6BT, United Kingdom
- 2MRC London Institute of Medical Sciences (LMS), London W12 0NN, United Kingdom
- 3Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom
- 4Department of Biochemistry, Sherbrooke, Université de Sherbrooke, Quebec J1H 5N4, Canada
- 5LMU Munich, Biomedical Center, 82152 Planegg-Martinsried near Munich, Germany
- 6Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom
- Corresponding author: j.bahler{at}ucl.ac.uk
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↵7 These authors contributed equally to this work.
Abstract
Long noncoding RNAs (lncRNAs), which are longer than 200 nucleotides but often unstable, contribute a substantial and diverse portion to pervasive noncoding transcriptomes. Most lncRNAs are poorly annotated and understood, although several play important roles in gene regulation and diseases. Here we systematically uncover and analyze lncRNAs in Schizosaccharomyces pombe. Based on RNA-seq data from twelve RNA-processing mutants and nine physiological conditions, we identify 5775 novel lncRNAs, nearly 4× the previously annotated lncRNAs. The expression of most lncRNAs becomes strongly induced under the genetic and physiological perturbations, most notably during late meiosis. Most lncRNAs are cryptic and suppressed by three RNA-processing pathways: the nuclear exosome, cytoplasmic exonuclease, and RNAi. Double-mutant analyses reveal substantial coordination and redundancy among these pathways. We classify lncRNAs by their dominant pathway into cryptic unstable transcripts (CUTs), Xrn1-sensitive unstable transcripts (XUTs), and Dicer-sensitive unstable transcripts (DUTs). XUTs and DUTs are enriched for antisense lncRNAs, while CUTs are often bidirectional and actively translated. The cytoplasmic exonuclease, along with RNAi, dampens the expression of thousands of lncRNAs and mRNAs that become induced during meiosis. Antisense lncRNA expression mostly negatively correlates with sense mRNA expression in the physiological, but not the genetic conditions. Intergenic and bidirectional lncRNAs emerge from nucleosome-depleted regions, upstream of positioned nucleosomes. Our results highlight both similarities and differences to lncRNA regulation in budding yeast. This broad survey of the lncRNA repertoire and characteristics in S. pombe, and the interwoven regulatory pathways that target lncRNAs, provides a rich framework for their further functional analyses.
Keywords
- pervasive transcription
- NMD pathway
- Schizosaccharomyces pombe
- RNA degradation
- antisense RNA
- cytoplasmic exonuclease
Footnotes
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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.065524.118.
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Freely available online through the RNA Open Access option.
- Received January 2, 2018.
- Accepted June 14, 2018.
This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.