Comparative analysis reveals genomic features of stress-induced transcriptional readthrough
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Significance: Cells and organisms live in constantly changing environments. Therefore, cells have evolved complex mechanisms to cope with physiological and environmental stresses. Many of these mechanisms involve transcriptional responses facilitating survival and adaptation. Recent evidence documents extensive transcriptional readthrough beyond annotated gene ends in response to stress, but the role and regulation of these downstream of gene-containing transcripts (DoGs) remain elusive. Here we report that induction of transcriptional readthrough is a hallmark of the mammalian stress response. We explore its causes and consequences in a genome-wide fashion, identifying thousands of readthrough transcripts that are induced in three different stress conditions. Our results suggest potential roles for this class of transcripts in the maintenance of open chromatin under stress.
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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, 2017
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556 · see citing works
Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters
Core, L. J., Waterfall, J. J., & Lis, J. T. (2008) · Science · doi:10.1126/science.1162228 · Cited by 1,986 · see citing works
A comparative encyclopedia of DNA elements in the mouse genome
Yue, F., Cheng, Y., Breschi, A., Vierstra, J., Wu, W., Ryba, T., Sandstrom, R., Ma, Z., Davis, C., Pope, B. D., et al. (2014) · Nature · doi:10.1038/nature13992 · Cited by 1,781 · see citing works
Antisense Transcription in the Mammalian Transcriptome
Katayama, S., Tomaru, Y., Kasukawa, T., Waki, K., Nakanishi, M., Nakamura, M., Nishida, H., Yap, C.-S., Suzuki, M., Kawai, J., et al. (2005) · Science · doi:10.1126/science.1112009 · Cited by 1,661 · see citing works
A compendium of RNA-binding motifs for decoding gene regulation
Ray, D., Kazan, H., Cook, K. B., Weirauch, M. T., Najafabadi, H. S., Li, X., Gueroussov, S., Albu, M., Zheng, H., Yang, A., et al. (2013) · Nature · doi:10.1038/nature12311 · Cited by 1,480 · see citing works
g:Profiler—a web server for functional interpretation of gene lists (2016 update)
Reimand, J., Arak, T., Adler, P., Kolberg, L., Reisberg, S., Peterson, H., & Vilo, J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw199 · Cited by 1,229 · see citing works
Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans
Adelman, K., & Lis, J. T. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3293 · Cited by 1,186 · see citing works
Charting histone modifications and the functional organization of mammalian genomes
Zhou, V. W., Goren, A., & Bernstein, B. E. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2905 · Cited by 1,147 · see citing works
Topologically associating domains are stable units of replication-timing regulation
Pope, B. D., Ryba, T., Dileep, V., Yue, F., Wu, W.-S., Denas, O., Vera, D. L., Wang, Y., Hansen, R. S., Canfield, T. K., et al. (2014) · Nature · doi:10.1038/nature13986 · Cited by 902 · see citing works
Controlling gene expression in response to stress
de Nadal, E., Ammerer, G., & Posas, F. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3055 · Cited by 720 · see citing works
Rougvie, A. E., & Lis, J. T. (1988) · Cell · doi:10.1016/s0092-8674(88)91087-2 · Cited by 680 · see citing works
TT-seq maps the human transient transcriptome
Schwalb, B., Michel, M., Zacher, B., Frühauf, K., Demel, C., Tresch, A., Gagneur, J., & Cramer, P. (2016) · Science · doi:10.1126/science.aad9841 · Cited by 548 · see citing works
Mammalian heat shock response and mechanisms underlying its genome-wide transcriptional regulation
Mahat, D. B., Salamanca, H. H., Duarte, F. M., Danko, C. G., & Lis, J. T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.025 · Cited by 426 · see citing works
Efficient Test and Visualization of Multi-Set Intersections
Wang, M., Zhao, Y., & Zhang, B. (2015) · Scientific Reports · doi:10.1038/srep16923 · Cited by 395 · see citing works
The splicing factor SC35 has an active role in transcriptional elongation
Lin, S., Coutinho-Mansfield, G., Wang, D., Pandit, S., & Fu, X. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1461 · Cited by 363 · see citing works
Widespread Regulation of Translation by Elongation Pausing in Heat Shock
Shalgi, R., Hurt, J. A., Krykbaeva, I., Taipale, M., Lindquist, S. L., & Burge, C. B. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.11.028 · Cited by 334 · see citing works
Self-citationTranscription termination by nuclear RNA polymerasesPreprint
Richard, P., & Manley, J. L. (2009) · Genes & Development · doi:10.1101/gad.1792809 · Cited by 326 · see citing works
A mammalian gene with introns instead of exons generating stable RNA products
Tycowski, K. T., Shu, M.-D., & STEITZ, J. A. (1996) · Nature · doi:10.1038/379464a0 · Cited by 318 · see citing works
Self-citationTranscription termination and the control of the transcriptome: why, where and how to stop
Porrúa, O., & Libri, D. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3943 · Cited by 314 · see citing works
Widespread disruption of host transcription termination in HSV-1 infection
Rutkowski, A. J., Erhard, F., L’Hernault, A., Bonfert, T., Schilhabel, M., Crump, C., Rosenstiel, P., Efstathiou, S., Zimmer, R., Friedel, C. C., et al. (2015) · Nature Communications · doi:10.1038/ncomms8126 · Cited by 275 · see citing works
Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution
Vierstra, J. D., Rynes, E., Sandstrom, R. S., Zhang, M., Canfield, T. K., Hansen, R. S., Stehling-Sun, S., Sabo, P. J., Byron, R., Humbert, R., et al. (2014) · Science · doi:10.1126/science.1246426 · Cited by 253 · see citing works
Signals for pre‐mRNA cleavage and polyadenylation
Tian, B., & Graber, J. H. (2011) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.116 · Cited by 237 · see citing works
Widespread Inducible Transcription Downstream of Human Genes
Vilborg, A., Passarelli, M. C., Yario, T. A., Tycowski, K. T., & Steitz, J. A. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.06.016 · Cited by 206 · see citing works
Self-citationShalgi, R., Hurt, J. A., Lindquist, S. L., & Burge, C. B. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.044 · Cited by 192 · see citing works
Self-citationGrosso, A. R., Leite, A. P., Carvalho, S., Matos, M. R., Martins, F. B., Vítor, A. C., Desterro, J. M., Carmo-Fonseca, M., & de Almeida, S. F. (2015) · eLife · doi:10.7554/elife.09214 · Cited by 152 · see citing works
Maza, I., Caspi, I., Zviran, A., Chomsky, E., Rais, Y., Viukov, S. V., Geula, S., Buenrostro, J. D., Weinberger, L., Krupalnik, V., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3270 · Cited by 133 · see citing works
Khorkova, O., Myers, A. J., Hsiao, J. H., & Wahlestedt, C. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu207 · Cited by 124 · see citing works
Destabilization of B2 RNA by EZH2 Activates the Stress Response
Zovoilis, A., Cifuentes‐Rojas, C., Chu, H.-P. C., Hernandez, A. J., & Lee, J. T. (2016) · Cell · doi:10.1016/j.cell.2016.11.041 · Cited by 95 · see citing works
PARP1 Represses PAP and Inhibits Polyadenylation during Heat Shock
Giammartino, D. C. D., Shi, Y., & Manley, J. L. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.11.005 · Cited by 77 · see citing works
Giannakakis, A., Zhang, J., Jenjaroenpun, P., Nama, S., Zainolabidin, N., Aau, M. Y., Yarmishyn, A. A., Vaz, C., Ivshina, A. V., Grinchuk, O. V., et al. (2015) · Scientific Reports · doi:10.1038/srep09737 · Cited by 69 · see citing works
Takii, R., Fujimoto, M., Tan, K., Takaki, E., Hayashida, N., Nakato, R., Shirahige, K., & Nakai, A. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00754-14 · Cited by 61 · see citing works
Readthrough transcription: How are DoGs made and what do they do?
Vilborg, A., & STEITZ, J. A. (2016) · RNA Biology · doi:10.1080/15476286.2016.1149680 · Cited by 56 · see citing works
Self-citationTranscription beyond borders has downstream consequences
Sönmez, Ç., & Dean, C. (2012) · RNA Biology · doi:10.4161/rna.18668 · Cited by 2 · see citing works
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RNA polymerase II speed: a key player in controlling and adapting transcriptome composition
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“…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…”
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- Authors
- Vilborg, A., Sabath, N., Wiesel, Y., Nathans, J., Levy-Adam, F., Yario, T. A., Steitz, J. A., & Shalgi, R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Technion – Israel Institute of Technology (IL)
- Department of Biochemistry, Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa 31096, Israel
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-09-19
- Volume
- 114
- Issue
- 40
- Pages
- E8362-E8371
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5635911
- OpenAlex
- W2755390119
- Cited by
- 131
- References
- 34
- Citations by year
- 2026: 13 · 2025: 10 · 2024: 20 · 2023: 16 · 2022: 20 · 2021: 19 · 2020: 10 · 2019: 9 · 2018: 13 · 2017: 1
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- California Institute of Technology
- National Institute of General Medical Sciences (R01GM026154)
- 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
- read-through transcription, stress response, heat shock, osmotic stress, oxidative stress, HSF1, antisense transcription, open chromatin, NIH3T3 cells, non-coding RNA
- MeSH terms
- Animals, Gene Expression Regulation, Osmotic Pressure, Transcription, Genetic, Genome, Oxidative Stress, Heat-Shock Response, Gene Expression Profiling, Genomics, NIH 3T3 Cells, Mice
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