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Cited by 78Genomics and Chromatin DynamicsRNA Research and SplicingCancer-related molecular mechanisms research

Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters

Open access
Chen, Yun, Pai, Athma A, Herudek, Jan, Lubas, Michal, Meola, Nicola, Järvelin, Aino I, Andersson, Robin, Pelechano, Vicent +3 more·2016·Nature Genetics
DOI 10.1038/ng.3616PMC PMC5008441

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Abstract

Abstract Mammalian transcriptomes are complex and formed by extensive promoter activity. In addition, gene promoters are largely divergent and initiate transcription of reverse-oriented promoter upstream transcripts (PROMPTs). Although PROMPTs are commonly terminated early, influenced by polyadenylation sites, promoters often cluster so that the divergent activity of one might impact another. Here, we find that the distance between promoters strongly correlates with the expression, stability and length of their associated PROMPTs. Adjacent promoters driving divergent mRNA transcription support PROMPT formation, but due to polyadenylation site constraints, these transcripts tend to spread into the neighboring mRNA on the same strand. This mechanism to derive new alternative mRNA transcription start sites (TSSs) is also evident at closely spaced promoters supporting convergent mRNA transcription. We suggest that basic building blocks of divergently transcribed core promoter pairs, in combination with the wealth of TSSs in mammalian genomes, provides a framework with which evolution shapes transcriptomes.

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  • Both active enhancers and promoters occupy nucleosome-free chromatin, bind RNAP and can be divergently transcribed.

    “Both active enhancers and promoters occupy nucleosome-free chromatin, bind RNAP and can be divergently transcribed [73, 236, 237].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [237]

    The Introduction describes divergent transcription at mammalian promoters and many enhancers. Results, under “Divergent TSSs have a common organization” (page unavailable), reports largely nucleosome-depleted regions between enhancer-RNA and promoter-transcript start sites. Our copy does not explicitly establish RNAP binding at both types of site, so that part of the claim is not supported. (LLM, conf=0.82)

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References 55 · Cited by 78

Research works printed but not linked: 47

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Authors
Chen, Y., Pai, A. A., Herudek, J., Lubas, M., Meola, N., Järvelin, A. I., Andersson, R., Pelechano, V., Steinmetz, L. M., Jensen, T. H., & Sandelin, A.
Affiliations
  • University of Copenhagen (DK)
  • Massachusetts Institute of Technology (US)
  • Aarhus University (DK)
  • European Molecular Biology Laboratory (DE)
  • Stanford Medicine (US)
Corresponding author
  • Jensen, Torben Heick
  • Sandelin, Albin
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2016-07-25
Volume
48
Issue
9
Pages
984-994
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.3616
PMC
PMC5008441
OpenAlex
W2506779270
Cited by
78
References
55
Citations by year
2026: 4 · 2025: 5 · 2024: 9 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 10 · 2018: 13 · 2017: 6 · 2016: 2
FWCI
5.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Genetics (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Innovationsfonden
  • Deutsche Forschungsgemeinschaft (1422/3-1)
  • Danmarks Grundforskningsfond (DNRF58)
  • Lundbeckfonden (R198-2015-172, R82-2010-6779)
  • Novo Nordisk
  • Novo Nordisk Fonden (NNF15OC0017010, NNF10SA1016550)
  • H. Lundbeck A/S
  • H2020 European Research Council (638273)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
prompting, divergent transcription, convergent transcription, alternative transcription start sites, polyadenylation sites, RNA metabolism, transcriptome evolution
MeSH terms
Humans, Models, Genetic, Promoter Regions, Genetic, RNA, Transcription, Genetic, Alternative Splicing, Transcription Initiation Site, Polyadenylation, High-Throughput Nucleotide Sequencing

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