Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast
- Wu Wei1,2,3,9,
- Bianca P. Hennig4,
- Jingwen Wang5,
- Yujie Zhang5,
- Ilaria Piazza6,
- Yerma Pareja Sanchez5,
- Christophe D. Chabbert4,10,
- Sophie H. Adjalley7,
- Lars M. Steinmetz3,4,8 and
- Vicent Pelechano5,9
- 1Center for Biomedical Informatics, Shanghai Engineering Research Center for Big Data in Pediatric Precision Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China;
- 2CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
- 3Stanford Genome Technology Center, Stanford University, Palo Alto, California 94304, USA;
- 4European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany;
- 5SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 65 Solna, Sweden;
- 6Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, 8093 Zürich, Switzerland;
- 7Wellcome Sanger Institute, Hinxton, CB10 1SA, United Kingdom;
- 8Department of Genetics, School of Medicine, Stanford University, Stanford, California 94305, USA
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↵9 These authors contributed equally to this work.
Abstract
Cryptic transcription is widespread and generates a heterogeneous group of RNA molecules of unknown function. To improve our understanding of cryptic transcription, we investigated their transcription start site (TSS) usage, chromatin organization, and posttranscriptional consequences in Saccharomyces cerevisiae. We show that TSSs of chromatin-sensitive internal cryptic transcripts retain comparable features of canonical TSSs in terms of DNA sequence, directionality, and chromatin accessibility. We define the 5′ and 3′ boundaries of cryptic transcripts and show that, contrary to RNA degradation–sensitive ones, they often overlap with the end of the gene, thereby using the canonical polyadenylation site, and associate to polyribosomes. We show that chromatin-sensitive cryptic transcripts can be recognized by ribosomes and may produce truncated polypeptides from downstream, in-frame start codons. Finally, we confirm the presence of the predicted polypeptides by reanalyzing N-terminal proteomic data sets. Our work suggests that a fraction of chromatin-sensitive internal cryptic promoters initiates the transcription of alternative truncated mRNA isoforms. The expression of these chromatin-sensitive isoforms is conserved from yeast to human, expanding the functional consequences of cryptic transcription and proteome complexity.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.243378.118.
- Received August 29, 2018.
- Accepted October 7, 2019.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
