NCBP1 electrophilic-stress signaling in the nucleus promotes alternatively-spliced S6K1 that dominantly inhibits global translation

Author:

Chang Dalu,Assari Mahdi,Suwathep Chananya,Sappakhaw Khomkrit,Uttamapinant Chayasith,Long Marcus. J. C.,Aye Yimon

Abstract

AbstractProteome synthesis is profoundly influenced by subcellular stress. However, both the nature of spatiotemporally-restricted cues and the underpinning local responders mediating these cues remain elusive. Unlocking these mechanisms requires an ability to functionally map in living cells locale-specific stress responders and simultaneously interrogate how a localized cue on specific local players contextually impacts proteome synthesisin trans. Here we resolve this prime problem by integrating precision localized electrophile delivery and genetic-code-expansion-based translation reporter tools. Among the four distinct subcellular locales examined, nuclear-targeted stress most prominently inhibits protein translation. We discovered that NCBP1—a nuclear-resident protein with multifaceted roles in eukaryotic mRNA-biogenesis—propagates this nuclear stress signal through a single cysteine (C436) among the 19 conserved, affecting 200 alternative-splicing events across 119 genes differentially-expressed in response to nuclear stress. Global protein-synthesis stall was choreographed by electrophile-labeled NCBP1(C436) triggering the production of alternatively-spliced S6-kinase, which we found to dominantly suppress protein translation.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3