Widespread Influence of 3'-End Structures on Mammalian mRNA Processing and Stability

Cell
Xuebing Wu, David P Bartel

Abstract

The physiological relevance of structures within mammalian mRNAs has been elusive, as these mRNAs are less folded in cells than in vitro and have predicted secondary structures no more stable than those of random sequences. Here, we investigate the possibility that mRNA structures facilitate the 3'-end processing of thousands of human mRNAs by juxtaposing poly(A) signals (PASs) and cleavage sites that are otherwise too far apart. We find that RNA structures are predicted to be more prevalent within these extended 3'-end regions than within PAS-upstream regions and indeed are substantially more folded within cells, as determined by intracellular probing. Analyses of thousands of ectopically expressed variants demonstrate that this folding both enhances processing and increases mRNA metabolic stability. Even folds with predicted stabilities resembling those of random sequences can enhance processing. Structure-controlled processing can also regulate neighboring gene expression. Thus, RNA structure has widespread roles in mammalian mRNA biogenesis and metabolism.

Citations

Dec 23, 2017·Human Genomics·Christopher Q ZhangEric S Ho
Jul 29, 2018·Nature Reviews. Genetics·Eric J StrobelJulius B Lucks
Oct 3, 2018·ELife·Justin RendlemanChristine Vogel
Oct 12, 2018·Journal of Biochemistry·Fengqian ShenLing Gao
Jan 9, 2019·Journal of Cellular Biochemistry·Zhuoxing LiuAibing Wu
Nov 16, 2018·Molecular Oncology·Christiane KlecMartin Pichler
Jan 19, 2019·Non-coding RNA·Irena Misiewicz-KrzeminskaNorma C Gutiérrez
Sep 19, 2019·Genome Research·Ilya Vainberg SlutskinEran Segal
Nov 30, 2018·Scientific Reports·Kodai MachidaHiroaki Imataka
Sep 27, 2019·Nature Reviews. Drug Discovery·Joana DesterroMaria Carmo-Fonseca
Oct 12, 2018·PloS One·Norberto Martins de Oliveira JuniorMarco Antonio Compagnoni
Jun 12, 2020·Transcription·Yadong SunLiang Tong
Sep 29, 2020·Nucleic Acids Research·Weiwei JinJing Gong
Oct 20, 2018·Nature Communications·Wan-Jung C LaiDmitri N Ermolenko
Apr 3, 2019·Cold Spring Harbor Perspectives in Biology·Marlene Belfort, Alan M Lambowitz
Sep 11, 2019·Current Protocols in Molecular Biology·Zarmik Moqtaderi, Joseph V Geisberg
Jan 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Matthew G CostalesMatthew D Disney
Aug 1, 2018·Nature Structural & Molecular Biology·Jean-Denis BeaudoinAntonio J Giraldez
Jul 1, 2020·Wiley Interdisciplinary Reviews. RNA·Dmitri N Ermolenko, David H Mathews
Nov 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Zhao SuSarah M Assmann
Nov 3, 2020·The Analyst·Riku HirataTakashi Ohtsuki
Dec 5, 2018·Cold Spring Harbor Perspectives in Biology·Zhipeng Lu, Howard Y Chang
Sep 19, 2020·International Journal of Molecular Sciences·Angelika AndrzejewskaKatarzyna Pachulska-Wieczorek
Aug 2, 2020·Chembiochem : a European Journal of Chemical Biology·Whitney E EnglandRobert C Spitale
Aug 4, 2019·Ecotoxicology and Environmental Safety·Congting YeQingshun Quinn Li
Dec 7, 2018·Methods : a Companion to Methods in Enzymology·Zhiye WangXiuren Zhang
Jan 24, 2021·Journal of Experimental Botany·Jiaying ZhuXiuren Zhang
Apr 1, 2021·Proceedings of the National Academy of Sciences of the United States of America·Seyed-Fakhreddin TorabiJoan A Steitz
Apr 18, 2021·Nature Communications·Svetlana KalmykovaDmitri Pervouchine
May 5, 2021·Trends in Biochemical Sciences·Huiyun Liu, Claire L Moore
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dominika VeselinyováMiroslava Rabajdová
Oct 25, 2017·Biochemistry·Dalen Chan, Robert C Spitale
Oct 6, 2021·Nature Biotechnology·James W NelsonDavid R Liu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.