The U6 snRNA m6 A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention

Cell
Kathryn E PendletonNicholas K Conrad

Abstract

Maintenance of proper levels of the methyl donor S-adenosylmethionine (SAM) is critical for a wide variety of biological processes. We demonstrate that the N6-adenosine methyltransferase METTL16 regulates expression of human MAT2A, which encodes the SAM synthetase expressed in most cells. Upon SAM depletion by methionine starvation, cells induce MAT2A expression by enhanced splicing of a retained intron. Induction requires METTL16 and its methylation substrate, a vertebrate conserved hairpin (hp1) in the MAT2A 3' UTR. Increasing METTL16 occupancy on the MAT2A 3' UTR is sufficient to induce efficient splicing. We propose that, under SAM-limiting conditions, METTL16 occupancy on hp1 increases due to inefficient enzymatic turnover, which promotes MAT2A splicing. We further show that METTL16 is the long-unknown methyltransferase for the U6 spliceosomal small nuclear RNA (snRNA). These observations suggest that the conserved U6 snRNA methyltransferase evolved an additional function in vertebrates to regulate SAM homeostasis.

Citations

Jan 26, 2018·RNA·Allison L DidychukDavid A Brow
Nov 11, 2017·International Journal of Molecular Sciences·Roland JacobTony Gutschner
Feb 15, 2018·International Journal of Molecular Sciences·Hsiang-Cheng ChiKwang-Huei Lin
Dec 1, 2017·Antioxidants & Redox Signaling·María A Pajares, Dolores Pérez-Sala
Feb 23, 2018·Leukemia·Alex C H WongJustin J-L Wong
Oct 25, 2017·Genome Biology·Phillip J HsuChuan He
Sep 5, 2017·Nature Structural & Molecular Biology·Raghu R EdupugantiMichiel Vermeulen
May 22, 2018·FEBS Letters·Philip Knuckles, Marc Bühler
Jun 20, 2018·Wiley Interdisciplinary Reviews. RNA·Helena Covelo-MolaresStepanka Vanacova
Jul 25, 2018·Journal of Cellular and Molecular Medicine·Liujia HeLiping Xie
Jun 6, 2018·Infection and Immunity·Jeffrey S BourgeoisDennis C Ko
Sep 27, 2018·Wiley Interdisciplinary Reviews. RNA·Hong-Chao DuanGuifang Jia
Jun 17, 2018·Biological Chemistry·Markus T Bohnsack, Katherine E Sloan
Oct 3, 2018·Angewandte Chemie·Maksim V SednevClaudia Höbartner
Sep 20, 2018·Annual Review of Genetics·Sigrid Nachtergaele, Chuan He
Oct 23, 2018·Chemistry : a European Journal·Katja Hartstock, Andrea Rentmeister
Jan 28, 2018·Cell Death & Disease·Dongjun DaiXian Wang
Feb 23, 2019·Molecular Biology Reports·Bing ChenFeng Xu
May 1, 2019·Nature Cell Biology·Shan XiaoLaixin Xia
May 8, 2019·Nature Medicine·Zhenxun WangWai Leong Tam
Sep 15, 2019·Nature Reviews. Molecular Cell Biology·Sara ZaccaraSamie R Jaffrey
Jul 10, 2019·Annual Review of Virology·Graham D WilliamsStacy M Horner
Feb 20, 2019·Nature Chemical Biology·Jan MauerSamie R Jaffrey
Jun 7, 2019·Current Opinion in Hematology·Zhenrui LiLinheng Li
Dec 11, 2019·Nature Chemical Biology·Jinghui SongChengqi Yi
Jul 25, 2019·Journal of Molecular Cell Biology·Marlene ReichelDorothee Staiger
Jan 16, 2020·PloS One·Daniel J NanceKyle D Mansfield
Jan 22, 2020·Wiley Interdisciplinary Reviews. RNA·Joshua D JonesKristin S Koutmou
Jan 29, 2020·Fish Physiology and Biochemistry·Wei PangXiaowu Chen
Jan 30, 2020·RNA Biology·Phensinee HaruehanroengraJia Sheng
Apr 9, 2020·Nucleic Acids Research·Tomohiko AoyamaKozo Tomita
May 1, 2019·Scientific Reports·Valentina V IgnatovaRobert Schneider
Mar 29, 2020·Genes & Development·Valentina V IgnatovaRobert Schneider
Sep 7, 2018·Journal of Virology·Brandon Tan, Shou-Jiang Gao
May 28, 2019·Nature Communications·Jiawei ZhaoRichard C Wang
May 23, 2020·Protein & Cell·Lin-Yong ZhaoChengqi Yi
May 23, 2020·Wiley Interdisciplinary Reviews. RNA·Jessica A Brown
May 14, 2020·RNA Biology·Daniele HaslerUtz Fischer

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