Differential effects of pre-mRNA splicing inhibitors on RNA polymerase II transcription

Author:

Tellier MichaelORCID,Ansa Gilbert,Murphy ShonaORCID

Abstract

SummaryThe production of eukaryotic mRNA requires transcription by RNA polymerase (pol) II and co-transcriptional processing, including capping, splicing, and cleavage and polyadenylation (CPA). Pol II can positively affect co-transcriptional processing through interaction of factors with its carboxyl terminal domain (CTD), comprising 52 repeats of the heptapeptide Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Small molecule inhibitors of the splicing factor SF3B1 cause loss of the transcription elongation factor P-TEFb from protein-coding gene templates and major transcription defects, indicating that splicing can, in turn, positively affect transcription. To understand better the relationship between pre-mRNA splicing and pol II transcription, we have investigated the effect of two other splicing inhibitors, Madrasin and Isoginkgetin, on transcription. We found that Madrasin rapidly inhibits pre-mRNA splicing, whereas Isoginkgetin affects transcription before any detectable effect on pre-mRNA splicing. Interestingly, we found that both of these small molecules promote general downregulation of transcription and global transcriptional readthrough, including on intronless and histone genes. Both small molecules affect the association of the mRNA CPA complex with chromatin, likely explaining the transcription termination defect. However, splicing inhibition is not necessarily associated with transcriptional readthrough as small molecule inhibitors of SF3B1 or knockdown of splicing factors do not cause a global transcription termination defect.

Publisher

Cold Spring Harbor Laboratory

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

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