A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus

Although some information is available for specific subsets of miRNAs and several factors have been shown to bind oligonucleotides (ONs), no general transport mechanism for these molecules has been identified to date. In this work, we demonstrate that the nuclear transport of ONs, siRNAs, and miRNAs...

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Autores principales: Castanotto, Daniela, Zhang, Xiaowei, Alluin, Jessica, Zhang, Xizhe, Rüger, Jacqueline, Armstrong, Brian, Rossi, John, Riggs, Arthur, Stein, C. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
PNAS Plus
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016802/
https://www.ncbi.nlm.nih.gov/pubmed/29866826
http://dx.doi.org/10.1073/pnas.1721346115
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author Castanotto, Daniela
Zhang, Xiaowei
Alluin, Jessica
Zhang, Xizhe
Rüger, Jacqueline
Armstrong, Brian
Rossi, John
Riggs, Arthur
Stein, C. A.
author_facet Castanotto, Daniela
Zhang, Xiaowei
Alluin, Jessica
Zhang, Xizhe
Rüger, Jacqueline
Armstrong, Brian
Rossi, John
Riggs, Arthur
Stein, C. A.
author_sort Castanotto, Daniela
collection PubMed
description Although some information is available for specific subsets of miRNAs and several factors have been shown to bind oligonucleotides (ONs), no general transport mechanism for these molecules has been identified to date. In this work, we demonstrate that the nuclear transport of ONs, siRNAs, and miRNAs responds to cellular stress. Furthermore, we have identified a stress-induced response complex (SIRC), which includes Ago-1 and Ago-2 in addition to the transcription and splicing regulators YB1, CTCF, FUS, Smad1, Smad3, and Smad4. The SIRC transports endogenous miRNAs, siRNAs, and ONs to the nucleus. We show that cellular stress can significantly increase ON- or siRNA-directed splicing switch events and endogenous miRNA targeting of nuclear RNAs.
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spelling pubmed-60168022018-06-26 A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus Castanotto, Daniela Zhang, Xiaowei Alluin, Jessica Zhang, Xizhe Rüger, Jacqueline Armstrong, Brian Rossi, John Riggs, Arthur Stein, C. A. Proc Natl Acad Sci U S A PNAS Plus Although some information is available for specific subsets of miRNAs and several factors have been shown to bind oligonucleotides (ONs), no general transport mechanism for these molecules has been identified to date. In this work, we demonstrate that the nuclear transport of ONs, siRNAs, and miRNAs responds to cellular stress. Furthermore, we have identified a stress-induced response complex (SIRC), which includes Ago-1 and Ago-2 in addition to the transcription and splicing regulators YB1, CTCF, FUS, Smad1, Smad3, and Smad4. The SIRC transports endogenous miRNAs, siRNAs, and ONs to the nucleus. We show that cellular stress can significantly increase ON- or siRNA-directed splicing switch events and endogenous miRNA targeting of nuclear RNAs. National Academy of Sciences 2018-06-19 2018-06-04 /pmc/articles/PMC6016802/ /pubmed/29866826 http://dx.doi.org/10.1073/pnas.1721346115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Castanotto, Daniela
Zhang, Xiaowei
Alluin, Jessica
Zhang, Xizhe
Rüger, Jacqueline
Armstrong, Brian
Rossi, John
Riggs, Arthur
Stein, C. A.
A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus
title A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus
title_full A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus
title_fullStr A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus
title_full_unstemmed A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus
title_short A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus
title_sort stress-induced response complex (sirc) shuttles mirnas, sirnas, and oligonucleotides to the nucleus
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016802/
https://www.ncbi.nlm.nih.gov/pubmed/29866826
http://dx.doi.org/10.1073/pnas.1721346115
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