Widespread Inducible Transcription Downstream of Human Genes
Open accessAbstract
Pervasive transcription of the human genome generates RNAs whose mode of formation and functions are largely uncharacterized. Here, we combine RNA-seq with detailed mechanistic studies to describe a transcript type derived from protein-coding genes. The resulting RNAs, which we call DoGs for downstream of gene containing transcripts, possess long non-coding regions (often >45 kb) and remain chromatin bound. DoGs are inducible by osmotic stress through an IP3 receptor signaling-dependent pathway, indicating active regulation. DoG levels are increased by decreased termination of the upstream transcript, a previously undescribed mechanism for rapid transcript induction. Relative depletion of polyA signals in DoG regions correlates with increased levels of DoGs after osmotic stress. We detect DoG transcription in several human cell lines and provide evidence for thousands of DoGs genome wide.
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Transcriptional read-through is induced downstream of thousands of genes in response to different kinds of stresses.
“Moreover, transcriptional read‐through is induced downstream of thousands of genes in response to different kinds of stresses (Rutkowski et al, 2015; Vilborg et al, 2015; Vilborg et al, 2017; Cardiello et al, 2018; Hennig et al, 2018) and has been proposed to play an important role in the stress response by reinforcing the nuclear scaffold integrity after nuclear stress (Vilborg et al, 2015).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Vilborg et al, 2015
The Discussion reports read-through transcripts downstream of as many as 10% of protein-coding genes in response to osmotic stress. Its ‘Potential functions of DoGs’ section also reports induction after heat shock, but only for three DoGs examined; it does not establish induction downstream of thousands of genes under different kinds of stress. Page numbers are not available in our copy. (LLM, conf=0.87)
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References 38 · Cited by 206
- Authors
- Vilborg, A., Passarelli, M. C., Yario, T. A., Tycowski, K. T., & Steitz, J. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Steitz, Joan A.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 59
- Issue
- 3
- Pages
- 449-461
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4530028
- OpenAlex
- W1882171616
- Cited by
- 206
- References
- 38
- Citations by year
- 2026: 20 · 2025: 14 · 2024: 25 · 2023: 21 · 2022: 25 · 2021: 21 · 2020: 21 · 2019: 9 · 2018: 24 · 2017: 14 · 2016: 9 · 2015: 3
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM026154, GM026154)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- pervasive transcription, long non-coding RNA, polyadenylation, osmotic stress, gene expression regulation
- MeSH terms
- Cell Line, Chromatin, Gene Expression Regulation, Humans, Osmotic Pressure, Poly A, Potassium Chloride, RNA, Transcription, Genetic, Signal Transduction, Genome, Human, Sequence Analysis, RNA, Inositol 1,4,5-Trisphosphate Receptors, RNA, Long Noncoding
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