7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress

Abstract Non-coding 7SL RNA is an ancestor to mammalian Alu and B1 SINE RNAs and is thought to function exclusively within the Signal Recognition Particle (SRP), aiding in the translocation of secretory proteins into the endoplasmic reticulum for export. Here, we discover a function of 7SL/SRP unrel...

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Main Authors: Bojan Bujisic, Hun-Goo Lee, Lilei Xu, Uri Weissbein, Carlos Rivera, Ivan Topisirovic, Jeannie T. Lee
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56351-6
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author Bojan Bujisic
Hun-Goo Lee
Lilei Xu
Uri Weissbein
Carlos Rivera
Ivan Topisirovic
Jeannie T. Lee
author_facet Bojan Bujisic
Hun-Goo Lee
Lilei Xu
Uri Weissbein
Carlos Rivera
Ivan Topisirovic
Jeannie T. Lee
author_sort Bojan Bujisic
collection DOAJ
description Abstract Non-coding 7SL RNA is an ancestor to mammalian Alu and B1 SINE RNAs and is thought to function exclusively within the Signal Recognition Particle (SRP), aiding in the translocation of secretory proteins into the endoplasmic reticulum for export. Here, we discover a function of 7SL/SRP unrelated to protein secretion. Under acute heat shock, 7SL and SRP together selectively arrest cellular transcription and translation machineries during early response to stress. Under thermal stress, 7SL is upregulated, accumulates in the nucleus, and binds to target genes repressed by heat shock. Concurrently, in the cytosol, SRP binds to ribosomes and inhibits new protein synthesis. Translational suppression occurs independently of the signal peptide and is abrogated by depleting SRP. Translation inhibition extends to the mitochondria, as nuclear-encoded genes with mitochondrial functions are enriched among SRP targets. Thus, apart from its role in protein export, 7SL/SRP orchestrates a global response to acute stress that encompasses the nucleus, cytosol, and mitochondria across transcription and translation.
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spelling doaj-art-84596da9fdad4ae084191cab11f6f0932025-08-20T02:48:12ZengNature PortfolioNature Communications2041-17232025-02-0116111910.1038/s41467-025-56351-67SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stressBojan Bujisic0Hun-Goo Lee1Lilei Xu2Uri Weissbein3Carlos Rivera4Ivan Topisirovic5Jeannie T. Lee6Department of Molecular Biology, Massachusetts General HospitalDepartment of Molecular Biology, Massachusetts General HospitalDepartment of Molecular Biology, Massachusetts General HospitalDepartment of Molecular Biology, Massachusetts General HospitalDepartment of Molecular Biology, Massachusetts General HospitalLady Davis Institute, Gerald Bronfman Department of Oncology and Departments of Biochemistry and Experimental Medicine, McGill UniversityDepartment of Molecular Biology, Massachusetts General HospitalAbstract Non-coding 7SL RNA is an ancestor to mammalian Alu and B1 SINE RNAs and is thought to function exclusively within the Signal Recognition Particle (SRP), aiding in the translocation of secretory proteins into the endoplasmic reticulum for export. Here, we discover a function of 7SL/SRP unrelated to protein secretion. Under acute heat shock, 7SL and SRP together selectively arrest cellular transcription and translation machineries during early response to stress. Under thermal stress, 7SL is upregulated, accumulates in the nucleus, and binds to target genes repressed by heat shock. Concurrently, in the cytosol, SRP binds to ribosomes and inhibits new protein synthesis. Translational suppression occurs independently of the signal peptide and is abrogated by depleting SRP. Translation inhibition extends to the mitochondria, as nuclear-encoded genes with mitochondrial functions are enriched among SRP targets. Thus, apart from its role in protein export, 7SL/SRP orchestrates a global response to acute stress that encompasses the nucleus, cytosol, and mitochondria across transcription and translation.https://doi.org/10.1038/s41467-025-56351-6
spellingShingle Bojan Bujisic
Hun-Goo Lee
Lilei Xu
Uri Weissbein
Carlos Rivera
Ivan Topisirovic
Jeannie T. Lee
7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress
Nature Communications
title 7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress
title_full 7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress
title_fullStr 7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress
title_full_unstemmed 7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress
title_short 7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress
title_sort 7sl rna and signal recognition particle orchestrate a global cellular response to acute thermal stress
url https://doi.org/10.1038/s41467-025-56351-6
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