METTL6 is a tRNA m


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
08 2020
Historique:
received: 19 09 2019
accepted: 14 07 2020
entrez: 14 9 2020
pubmed: 15 9 2020
medline: 13 4 2022
Statut: epublish

Résumé

Recently, covalent modifications of RNA, such as methylation, have emerged as key regulators of all aspects of RNA biology and have been implicated in numerous diseases, for instance, cancer. Here, we undertook a combination of in vitro and in vivo screens to test 78 potential methyltransferases for their roles in hepatocellular carcinoma (HCC) cell proliferation. We identified methyltransferase-like protein 6 (METTL6) as a crucial regulator of tumor cell growth. We show that METTL6 is a bona fide transfer RNA (tRNA) methyltransferase, catalyzing the formation of 3-methylcytidine at C32 of specific serine tRNA isoacceptors. Deletion of

Identifiants

pubmed: 32923617
doi: 10.1126/sciadv.aaz4551
pii: aaz4551
pmc: PMC7449687
doi:

Substances chimiques

RNA 63231-63-0
RNA, Transfer 9014-25-9
METTL6 protein, human EC 2.1.1.-
Methyltransferases EC 2.1.1.-
tRNA Methyltransferases EC 2.1.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eaaz4551

Subventions

Organisme : NICHD NIH HHS
ID : R01 HD080224
Pays : United States

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Références

Nature. 2018 Jun;558(7711):605-609
pubmed: 29925953
Genome Biol. 2014;15(12):550
pubmed: 25516281
Cell. 2011 Nov 11;147(4):789-802
pubmed: 22056041
Cell Res. 2018 May;28(5):507-517
pubmed: 29686311
Nucleic Acids Res. 2018 Jan 4;46(D1):D303-D307
pubmed: 29106616
Mol Cell. 2019 Jun 20;74(6):1278-1290.e9
pubmed: 31031083
Elife. 2016 Apr 27;5:
pubmed: 27117520
Nucleic Acids Res. 2015 Jan;43(1):e2
pubmed: 25505164
Cell. 2013 Sep 12;154(6):1380-9
pubmed: 23992846
Nucleic Acids Res. 2015 Sep 30;43(17):e112
pubmed: 26007658
Clin Cancer Res. 2011 Sep 1;17(17):5801-11
pubmed: 21775533
Cell Res. 2018 Apr;28(4):395-404
pubmed: 29463900
Bioinformatics. 2010 Sep 1;26(17):2176-82
pubmed: 20610611
Nat Methods. 2015 Aug;12(8):767-72
pubmed: 26121403
J Mol Med (Berl). 2019 Nov;97(11):1535-1545
pubmed: 31463732
Nat Methods. 2015 Sep;12(9):835-837
pubmed: 26214130
Nucleic Acids Res. 2019 Jan 8;47(D1):D941-D947
pubmed: 30371878
J Biol Chem. 2017 Sep 1;292(35):14695-14703
pubmed: 28655767
Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102
pubmed: 28407145
RNA. 2016 Nov;22(11):1771-1784
pubmed: 27613580
Nature. 2011 Aug 24;477(7364):340-3
pubmed: 21866103
Mol Cell. 2019 May 16;74(4):640-650
pubmed: 31100245
Nature. 2017 Dec 7;552(7683):126-131
pubmed: 29186125
Nucleic Acids Res. 2017 Jan 25;45(2):e6
pubmed: 27638886
Genes (Basel). 2019 Jan 05;10(1):
pubmed: 30621251
Mol Cell. 2018 Jul 19;71(2):244-255.e5
pubmed: 29983320
RNA. 2011 Jun;17(6):1100-10
pubmed: 21518804
Science. 2009 Apr 10;324(5924):218-23
pubmed: 19213877
Cell Res. 2011 Mar;21(3):381-95
pubmed: 21321607
Trends Mol Med. 2014 Jun;20(6):306-14
pubmed: 24581449
Nat Chem Biol. 2019 Jan;15(1):88-94
pubmed: 30531910
Bioinformatics. 2013 Sep 1;29(17):2146-52
pubmed: 23821648
Methods. 2019 Mar 1;156:91-101
pubmed: 30395967
Nature. 2016 Jun 15;534(7607):335-40
pubmed: 27306184
Breast Cancer Res. 2008;10(4):R65
pubmed: 18662380
Nat Genet. 2014 Oct;46(10):1051-9
pubmed: 25151356
Nucleic Acids Res. 2015 Nov 16;43(20):9950-64
pubmed: 26365242
Int J Mol Sci. 2018 Nov 24;19(12):
pubmed: 30477220
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Sci Rep. 2019 Apr 29;9(1):6584
pubmed: 31036863
RNA. 2017 Sep;23(9):1365-1375
pubmed: 28546148
Nat Commun. 2019 Jan 3;10(1):19
pubmed: 30604761
Mol Cell. 2017 Dec 7;68(5):978-992.e4
pubmed: 29198561
Nat Cell Biol. 2019 May;21(5):552-559
pubmed: 31048770
Methods Enzymol. 2015;560:29-71
pubmed: 26253965
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
RNA. 2015 Apr;21(4):703-4
pubmed: 25780199
Cell. 2015 Jun 18;161(7):1606-18
pubmed: 26052047
FEBS Lett. 1998 Sep 25;436(1):99-103
pubmed: 9771901
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
RNA. 2011 Jun;17(6):1111-9
pubmed: 21518805
Curr Protoc Mouse Biol. 2013 Jun 01;3(2):69-100
pubmed: 26069059
Cell. 2018 May 17;173(5):1204-1216.e26
pubmed: 29628141
Nature. 2015 Mar 26;519(7544):482-5
pubmed: 25799998
Methods. 2011 Feb;53(2):120-35
pubmed: 20708688
Nat Rev Mol Cell Biol. 2005 Feb;6(2):139-49
pubmed: 15688000
Cancer Lett. 2020 Apr 1;474:127-137
pubmed: 31991154

Auteurs

Valentina V Ignatova (VV)

Institute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Steffen Kaiser (S)

Chemical Faculty, Ludwig-Maximilians Universität München, Munich, Germany.

Jessica Sook Yuin Ho (JSY)

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Xinyang Bing (X)

University of Massachusetts Medical School, Worcester, MA 01605, USA.

Paul Stolz (P)

Department of Biology II, Human Biology and BioImaging, Ludwig-Maximilians Universität München, Munich, Germany.

Ying Xim Tan (YX)

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.

Chee Leng Lee (CL)

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.

Florence Pik Hoon Gay (FPH)

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.

Palma Rico Lastres (PR)

Institute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Raffaele Gerlini (R)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.

Birgit Rathkolb (B)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-University München, Munich, Germany.

Antonio Aguilar-Pimentel (A)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Adrián Sanz-Moreno (A)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Tanja Klein-Rodewald (T)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Julia Calzada-Wack (J)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Emil Ibragimov (E)

Institute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Magdalena Valenta (M)

Institute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Saulius Lukauskas (S)

Institute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Andrea Pavesi (A)

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.

Susan Marschall (S)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Stefanie Leuchtenberger (S)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Helmut Fuchs (H)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Valerie Gailus-Durner (V)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.

Martin Hrabe de Angelis (MH)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Chair of Experimental Genetics, School of Life Science Weihenstephan, Technische Universität München, 85354 Freising, Germany.

Sebastian Bultmann (S)

Department of Biology II, Human Biology and BioImaging, Ludwig-Maximilians Universität München, Munich, Germany.

Oliver J Rando (OJ)

University of Massachusetts Medical School, Worcester, MA 01605, USA.

Ernesto Guccione (E)

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Stefanie M Kellner (SM)

Chemical Faculty, Ludwig-Maximilians Universität München, Munich, Germany.

Robert Schneider (R)

Institute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Faculty of Biology, Ludwig-Maximilians Universität München, Munich, Germany.

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