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This research aims to understand how heat shock affects RNA polymerase II and termination processes during transcription.

February 28, 2026Open Access

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CPSF73 activation and 3′ RNA polymerase II pausing are lost during readthrough transcription after heat shock

Key Points

This research aims to understand how heat shock affects RNA polymerase II and termination processes during transcription.
Analyzed effects of heat shock on RNA polymerase II activity across multiple genes.
Assessed phosphorylation levels at the C-terminal domain of Pol II.
Examined endonucleolytic cleavage of nascent transcripts.
Tested the activator RBBP6 for CPSF73 activity during heat shock.
Heat shock induced significant readthrough transcription across thousands of genes.
Pol II pausing was lost following transcription termination sites post heat shock.
Increased phosphorylation of Tyr1 and Ser2 in Pol II was noted, particularly attenuated at readthrough genes.
CPSF73's endonucleolytic cleavage function was dysfunctional at readthrough genes but CPSF73 remained present.
RBBP6 overexpression during heat shock restored normal cleavage and reduced readthrough transcription.

Abstract

Summary Environmental stresses induce RNA polymerase II (Pol II) to read through normal termination sites at mRNA genes using unknown mechanisms. We observe strong readthrough transcription downstream of thousands of genes after heat shock. Additionally, Pol II no longer pauses after the 3′ ends of genes. Heat shock also increases phosphorylation of Tyr1 and Ser2 residues in the Pol II C-terminal domain (CTD) at the 3′ ends of genes, which is attenuated at genes with readthrough transcription. Endonucleolytic cleavage of the nascent transcript, key to normal termination, is defective at readthrough genes after heat shock. However, CPSF73, the endonuclease responsible, remains present. Overexpressing an activator of CPSF73, RBBP6, during heat shock rescues the loss of cleavage and dampens readthrough transcription. Together, our results show that heat shock alters Pol II speed, CTD phosphorylation, and CPSF73 activity via RBBP6, contributing to a multifaceted mechanism that enables readthrough of termination sites during cellular stress.

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Cite This Study

Walsh et al. (Thu,) studied this question.

synapsesocial.com/papers/69a286850a974eb0d3c017ef https://doi.org/https://doi.org/10.1016/j.celrep.2026.117039

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