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Chromatin-sensitive cryptic promoters encode alternative protein isoforms in yeast

View ORCID ProfileWu Wei, View ORCID ProfileBianca P. Hennig, View ORCID ProfileJingwen Wang, View ORCID ProfileYujie Zhang, View ORCID ProfileIlaria Piazza, View ORCID ProfileYerma Pareja Sanchez, View ORCID ProfileChristophe D. Chabbert, View ORCID ProfileSophie H. Adjalley, View ORCID ProfileLars M. Steinmetz, View ORCID ProfileVicent Pelechano
doi: https://doi.org/10.1101/403543
Wu Wei
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, CA, USA
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  • For correspondence: vicente.pelechano.garcia@ki.se wuwei@picb.ac.cn larsms@embl.de
Bianca P. Hennig
4European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
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Jingwen Wang
5SciLifeLab, Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet, Solna, Sweden
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Yujie Zhang
5SciLifeLab, Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet, Solna, Sweden
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Ilaria Piazza
6Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland
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Yerma Pareja Sanchez
5SciLifeLab, Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet, Solna, Sweden
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Christophe D. Chabbert
4European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
9Roche Innovation Center Zurich, Wagistrasse 10, 8952 Schlieren, Switzerland
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Sophie H. Adjalley
7Wellcome Sanger Institute, Hinxton, UK
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Lars M. Steinmetz
3Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA
4European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
8Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA
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  • For correspondence: vicente.pelechano.garcia@ki.se wuwei@picb.ac.cn larsms@embl.de
Vicent Pelechano
5SciLifeLab, Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet, Solna, Sweden
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  • ORCID record for Vicent Pelechano
  • For correspondence: vicente.pelechano.garcia@ki.se wuwei@picb.ac.cn larsms@embl.de
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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 usage, chromatin organization and post-transcriptional consequences in Saccharomyces cerevisiae. We show that transcription start sites (TSSs) of chromatin-sensitive internal cryptic transcripts retain comparable features of canonical TSSs in terms of DNA sequence, directionality and chromatin accessibility. We degine 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 congirm the presence of the predicted polypeptides by reanalyzing N-terminal proteomic datasets. Our work suggests that a fraction of chromatin-sensitive internal cryptic promoters are in fact 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

  • We have added new confirmatory data regarding the existence of the predicted truncated peptides by N-terminal COFRADIC. We have also added an extended comparison with the spt6-1004 dataset from Doris et al 2018 (Mol Cell).

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 12, 2019.
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Chromatin-sensitive cryptic promoters encode alternative protein isoforms in yeast
Wu Wei, Bianca P. Hennig, Jingwen Wang, Yujie Zhang, Ilaria Piazza, Yerma Pareja Sanchez, Christophe D. Chabbert, Sophie H. Adjalley, Lars M. Steinmetz, Vicent Pelechano
bioRxiv 403543; doi: https://doi.org/10.1101/403543
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Chromatin-sensitive cryptic promoters encode alternative protein isoforms in yeast
Wu Wei, Bianca P. Hennig, Jingwen Wang, Yujie Zhang, Ilaria Piazza, Yerma Pareja Sanchez, Christophe D. Chabbert, Sophie H. Adjalley, Lars M. Steinmetz, Vicent Pelechano
bioRxiv 403543; doi: https://doi.org/10.1101/403543

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