Nuclear stability and transcriptional directionality separate functionally distinct RNA species
Open accessPublished version of a preprint
Abstract
ABSTRACT Mammalian genomes are pervasively transcribed, yielding a complex transcriptome with high variability in composition and cellular abundance. While recent efforts have identified thousands of new long non-coding (lnc) RNAs and demonstrated a complex transcriptional repertoire produced by protein-coding (pc) genes, limited progress has been made in distinguishing functional RNA from spurious transcription events. This is partly due to present RNA classification, which is typically based on technical rather than biochemical criteria. Here we devise a strategy to systematically categorize human RNAs by their sensitivity to the ribonucleolytic RNA exosome complex and by the nature of their transcription initiation. These measures are surprisingly effective at correctly classifying annotated transcripts, including lncRNAs of known function. The approach also identifies uncharacterized stable lncRNAs, hidden among a vast majority of unstable transcripts. The predictive power of the approach promises to streamline the functional analysis of known and novel RNAs.
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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 [236]
The paper states that human protein-coding gene promoters and enhancers can be divergently transcribed (Abstract) and analyzes transcribed DNase-hypersensitive sites associated with promoters and enhancers (Directional bias and exosome sensitivity discern RNA biotypes; page unavailable). Our copy does not establish the more specific claims that both occupy nucleosome-free chromatin and bind RNAP. (LLM, conf=0.82)
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Cites
Landscape of transcription in human cells
Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., et al. (2012) · Nature · doi:10.1038/nature11233 · Cited by 5,187 · see citing works
An atlas of active enhancers across human cell types and tissues
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Andersson, R. (2015) · BioEssays · doi:10.1002/bies.201400162 · Cited by 127 · see citing works
Self-citationTranscriptional enhancers and their communication with gene promoters
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- Authors
- Andersson, R., Refsing Andersen, P., Valen, E., Core, L. J., Bornholdt, J., Boyd, M., Heick Jensen, T., & Sandelin, A.
- Affiliations
- University of Copenhagen (DK)
- Harvard University (US)
- University of Connecticut (US)
- Corresponding author
- Sandelin, Albin
- Venue
- Nature Communications
- Published
- 2014-11-12
- Volume
- 5
- Issue
- 1
- Pages
- 5336-5336
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2023375875
- Cited by
- 171
- References
- 6
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 7 · 2023: 14 · 2022: 21 · 2021: 13 · 2020: 19 · 2019: 15 · 2018: 24 · 2017: 16 · 2016: 14 · 2015: 13 · 2014: 3
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Kræftens Bekæmpelse
- National Research Foundation
- Danmarks Grundforskningsfond (DNRF58)
- Lundbeckfonden (R82-2010-6779)
- Novo Nordisk
- Novo Nordisk Fonden (NNF12OC0001211)
- H. Lundbeck A/S
- National Institutes of Health (GM025232)
- National Institute of General Medical Sciences (GM025232)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- RNA stability, long non-coding RNA, RNA exosome, transcription initiation, RNA classification, mammalian transcriptome
- MeSH terms
- HeLa Cells, Humans, Promoter Regions, Genetic, RNA, Transcription, Genetic, RNA Stability, RNA, Untranslated, Exosomes, Transcription Initiation, Genetic
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