Heat shock induces premature transcript termination and reconfigures the human transcriptome

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Heat shock induces premature transcript termination and reconfigures the human transcriptome. / Cugusi, Simona; Mitter, Richard; Kelly, Gavin P.; Walker, Jane; Han, Zhong; Pisano, Paola; Wierer, Michael; Stewart, Aengus; Svejstrup, Jesper Q.

In: Molecular Cell, Vol. 82, No. 8, 2022, p. 1573-1588.e10.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Cugusi, S, Mitter, R, Kelly, GP, Walker, J, Han, Z, Pisano, P, Wierer, M, Stewart, A & Svejstrup, JQ 2022, 'Heat shock induces premature transcript termination and reconfigures the human transcriptome', Molecular Cell, vol. 82, no. 8, pp. 1573-1588.e10. https://doi.org/10.1016/j.molcel.2022.01.007

APA

Cugusi, S., Mitter, R., Kelly, G. P., Walker, J., Han, Z., Pisano, P., Wierer, M., Stewart, A., & Svejstrup, J. Q. (2022). Heat shock induces premature transcript termination and reconfigures the human transcriptome. Molecular Cell, 82(8), 1573-1588.e10. https://doi.org/10.1016/j.molcel.2022.01.007

Vancouver

Cugusi S, Mitter R, Kelly GP, Walker J, Han Z, Pisano P et al. Heat shock induces premature transcript termination and reconfigures the human transcriptome. Molecular Cell. 2022;82(8):1573-1588.e10. https://doi.org/10.1016/j.molcel.2022.01.007

Author

Cugusi, Simona ; Mitter, Richard ; Kelly, Gavin P. ; Walker, Jane ; Han, Zhong ; Pisano, Paola ; Wierer, Michael ; Stewart, Aengus ; Svejstrup, Jesper Q. / Heat shock induces premature transcript termination and reconfigures the human transcriptome. In: Molecular Cell. 2022 ; Vol. 82, No. 8. pp. 1573-1588.e10.

Bibtex

@article{ef04157d766546bfa8465be197ecd524,
title = "Heat shock induces premature transcript termination and reconfigures the human transcriptome",
abstract = "The heat shock (HS) response involves rapid induction of HS genes, whereas transcriptional repression is established more slowly at most other genes. Previous data suggested that such repression results from inhibition of RNA polymerase II (RNAPII) pause release, but here, we show that HS strongly affects other phases of the transcription cycle. Intriguingly, while elongation rates increase upon HS, processivity markedly decreases, so that RNAPII frequently fails to reach the end of genes. Indeed, HS results in widespread premature transcript termination at cryptic, intronic polyadenylation (IPA) sites near gene 5′-ends, likely via inhibition of U1 telescripting. This results in dramatic reconfiguration of the human transcriptome with production of new, previously unannotated, short mRNAs that accumulate in the nucleus. Together, these results shed new light on the basic transcription mechanisms induced by growth at elevated temperature and show that a genome-wide shift toward usage of IPA sites can occur under physiological conditions.",
keywords = "alternative polyadenylation, CDK9, CPSF3, cryptic polyadenylation sites, elongation, heat shock, pause release, premature termination, pTEFb, SCAF4, SCAF8, telescripting, transcriptional repression, TT-seq, U1 snRNA",
author = "Simona Cugusi and Richard Mitter and Kelly, {Gavin P.} and Jane Walker and Zhong Han and Paola Pisano and Michael Wierer and Aengus Stewart and Svejstrup, {Jesper Q.}",
note = "Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
doi = "10.1016/j.molcel.2022.01.007",
language = "English",
volume = "82",
pages = "1573--1588.e10",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "8",

}

RIS

TY - JOUR

T1 - Heat shock induces premature transcript termination and reconfigures the human transcriptome

AU - Cugusi, Simona

AU - Mitter, Richard

AU - Kelly, Gavin P.

AU - Walker, Jane

AU - Han, Zhong

AU - Pisano, Paola

AU - Wierer, Michael

AU - Stewart, Aengus

AU - Svejstrup, Jesper Q.

N1 - Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - The heat shock (HS) response involves rapid induction of HS genes, whereas transcriptional repression is established more slowly at most other genes. Previous data suggested that such repression results from inhibition of RNA polymerase II (RNAPII) pause release, but here, we show that HS strongly affects other phases of the transcription cycle. Intriguingly, while elongation rates increase upon HS, processivity markedly decreases, so that RNAPII frequently fails to reach the end of genes. Indeed, HS results in widespread premature transcript termination at cryptic, intronic polyadenylation (IPA) sites near gene 5′-ends, likely via inhibition of U1 telescripting. This results in dramatic reconfiguration of the human transcriptome with production of new, previously unannotated, short mRNAs that accumulate in the nucleus. Together, these results shed new light on the basic transcription mechanisms induced by growth at elevated temperature and show that a genome-wide shift toward usage of IPA sites can occur under physiological conditions.

AB - The heat shock (HS) response involves rapid induction of HS genes, whereas transcriptional repression is established more slowly at most other genes. Previous data suggested that such repression results from inhibition of RNA polymerase II (RNAPII) pause release, but here, we show that HS strongly affects other phases of the transcription cycle. Intriguingly, while elongation rates increase upon HS, processivity markedly decreases, so that RNAPII frequently fails to reach the end of genes. Indeed, HS results in widespread premature transcript termination at cryptic, intronic polyadenylation (IPA) sites near gene 5′-ends, likely via inhibition of U1 telescripting. This results in dramatic reconfiguration of the human transcriptome with production of new, previously unannotated, short mRNAs that accumulate in the nucleus. Together, these results shed new light on the basic transcription mechanisms induced by growth at elevated temperature and show that a genome-wide shift toward usage of IPA sites can occur under physiological conditions.

KW - alternative polyadenylation

KW - CDK9

KW - CPSF3

KW - cryptic polyadenylation sites

KW - elongation

KW - heat shock

KW - pause release

KW - premature termination

KW - pTEFb

KW - SCAF4

KW - SCAF8

KW - telescripting

KW - transcriptional repression

KW - TT-seq

KW - U1 snRNA

U2 - 10.1016/j.molcel.2022.01.007

DO - 10.1016/j.molcel.2022.01.007

M3 - Journal article

C2 - 35114099

AN - SCOPUS:85124913219

VL - 82

SP - 1573-1588.e10

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 8

ER -

ID: 298630181