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

被引：33

作者：

Castanotto, Daniela ^{[1
]}

Zhang, Xiaowei ^{[1
]}

Alluin, Jessica ^{[2
]}

Zhang, Xizhe ^{[3
]}

Rueger, Jacqueline ^{[1
]}

Armstrong, Brian ^{[4
]}

Rossi, John ^{[2
]}

Riggs, Arthur ^{[3
]}

Stein, C. A. ^{[1
,2
]}

机构：

[1] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Dept Mol & Cellular Biol, Duarte, CA 91010 USA

[3] City Hope Natl Med Ctr, Dept Diabet & Metab Dis, Duarte, CA 91010 USA

[4] City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 25期

关键词：

miRNA; SSO; stress granules; FUS; YB1; BOX-BINDING PROTEIN-1; RNA INTERFERENCE; MESSENGER-RNA; PHOSPHOROTHIOATE OLIGONUCLEOTIDES; ANTISENSE OLIGONUCLEOTIDES; OXIDATIVE STRESS; MAMMALIAN-CELLS; GRANULES; YB-1; BODIES;

D O I：

10.1073/pnas.1721346115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：E5756 / E5765

页数：10

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