A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription.
RNA modification
cancer metastasis
tRNA
transcription
translation
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 03 2022
15 03 2022
Historique:
revised:
19
10
2021
received:
22
04
2021
accepted:
29
10
2021
pubmed:
2
12
2021
medline:
6
5
2022
entrez:
1
12
2021
Statut:
ppublish
Résumé
Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation.
Identifiants
pubmed: 34850409
doi: 10.15252/embj.2021108544
pmc: PMC8922252
doi:
Substances chimiques
RNA-Binding Proteins
0
RNA
63231-63-0
RNA, Transfer
9014-25-9
tRNA Methyltransferases
EC 2.1.1.-
Banques de données
GEO
['GSE166278', 'GSE166274', 'GSE166276', 'GSE166270']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e108544Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
Références
Nature. 2018 Jun;558(7711):605-609
pubmed: 29925953
RNA. 2015 Sep;21(9):1532-43
pubmed: 26160102
Hum Mol Genet. 2018 Apr 1;27(7):1276-1289
pubmed: 29415125
J Biol Chem. 2018 Jul 20;293(29):11401-11414
pubmed: 29871931
BMC Cancer. 2007 Mar 27;7:55
pubmed: 17389037
Nature. 2017 Feb 22;542(7642):494-497
pubmed: 28230119
Cell. 2016 Oct 20;167(3):816-828.e16
pubmed: 27745969
Cell. 2015 Jun 18;161(7):1606-18
pubmed: 26052047
Cell Stem Cell. 2016 May 5;18(5):637-52
pubmed: 26996597
Methods. 2014 Feb;65(3):274-87
pubmed: 24184352
Nature. 2021 Mar;591(7849):317-321
pubmed: 33505026
DNA Cell Biol. 2012 Apr;31(4):434-54
pubmed: 22191691
J Exp Bot. 2017 Mar 1;68(7):1479-1491
pubmed: 28369540
Cell. 2015 May 7;161(4):790-802
pubmed: 25957686
Nature. 2021 Mar;591(7849):312-316
pubmed: 33442060
PLoS One. 2020 Feb 13;15(2):e0229103
pubmed: 32053677
Structure. 2009 Feb 13;17(2):294-302
pubmed: 19217400
Cell. 2019 Jun 27;178(1):107-121.e18
pubmed: 31251911
J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
pubmed: 16478745
Nat Methods. 2015 Sep;12(9):835-837
pubmed: 26214130
Nat Methods. 2015 Sep;12(9):879-84
pubmed: 26237225
Genes (Basel). 2018 May 10;9(5):
pubmed: 29748504
J Mol Biol. 1993 Sep 20;233(2):191-202
pubmed: 8377197
FEBS Lett. 2014 Nov 28;588(23):4297-304
pubmed: 25220675
Cell Death Differ. 2015 Feb;22(2):336-50
pubmed: 25301070
Mol Cell Biol. 2014 Jul;34(13):2450-63
pubmed: 24752898
EMBO J. 2022 Mar 15;41(6):e108544
pubmed: 34850409
Science. 2016 Jan 22;351(6271):397-400
pubmed: 26721680
Bioinformatics. 2008 Oct 15;24(20):2277-80
pubmed: 18703587
Science. 2014 Jul 25;345(6195):455-9
pubmed: 25061210
Front Cell Dev Biol. 2020 Jul 08;8:605
pubmed: 32733895
Science. 2016 Jan 22;351(6271):391-396
pubmed: 26721685
Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14306-14311
pubmed: 27849601
Nat Cell Biol. 2018 May;20(5):535-540
pubmed: 29695786
Cell. 2009 Jul 23;138(2):215-9
pubmed: 19632169
Cancer Res. 2015 Mar 15;75(6):1009-20
pubmed: 25600647
Oncol Rep. 2014 Jan;31(1):197-201
pubmed: 24173679
Cancer Res. 2008 May 1;68(9):3108-14
pubmed: 18451135
J Biol Chem. 2016 Nov 11;291(46):24293-24303
pubmed: 27703015
J Mol Model. 2010 Mar;16(3):599-606
pubmed: 19697067
Nat Rev Genet. 2015 Feb;16(2):98-112
pubmed: 25534324
Trends Mol Med. 2014 Jun;20(6):306-14
pubmed: 24581449
Mol Cell. 2011 Aug 19;43(4):613-23
pubmed: 21855800
Cell Res. 2009 Feb;19(2):156-72
pubmed: 19153598
Trends Cancer. 2017 Apr;3(4):249-252
pubmed: 28718436
Cell Death Dis. 2014 Oct 02;5:e1443
pubmed: 25275602
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1404-9
pubmed: 23297232
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
pubmed: 24556840
J Clin Invest. 2016 Jan;126(1):137-50
pubmed: 26619117
J Cell Commun Signal. 2018 Dec;12(4):709-721
pubmed: 29480433
Cell Res. 2016 Apr;26(4):395-6
pubmed: 26902286
Nat Rev Cancer. 2020 Jun;20(6):303-322
pubmed: 32300195
EMBO J. 2018 Jun 15;37(12):
pubmed: 29769402
Oncogene. 1997 May 1;14(17):2091-8
pubmed: 9160889
J Clin Invest. 2017 Oct 2;127(10):3675-3688
pubmed: 28872461
Nat Commun. 2017 Nov 15;8(1):1524
pubmed: 29142256
RNA Biol. 2020 Aug;17(8):1214-1222
pubmed: 32116113
Nature. 2020 Apr;580(7803):402-408
pubmed: 32296183
Science. 2018 Sep 28;361(6409):1346-1349
pubmed: 30262497
Nature. 2003 Nov 6;426(6962):96-100
pubmed: 14603324
Nucleic Acids Res. 2019 Mar 18;47(5):2533-2545
pubmed: 30541109
Mol Cell Biol. 2017 Oct 13;37(21):
pubmed: 28784718
Proteomics. 2013 Oct;13(20):2989-97
pubmed: 23970329
Nat Rev Mol Cell Biol. 2018 Jan;19(1):20-30
pubmed: 29018283
Cell. 2016 Jun 2;165(6):1416-1427
pubmed: 27259150
Cell. 2018 May 17;173(5):1204-1216.e26
pubmed: 29628141
Nat Rev Mol Cell Biol. 2018 Jan;19(1):45-58
pubmed: 28875994
J Exp Med. 2016 Oct 17;213(11):2503-2523
pubmed: 27811057
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1241-6
pubmed: 11818576
Science. 2020 Jan 31;367(6477):580-586
pubmed: 31949099
Bioessays. 2017 Mar;39(3):
pubmed: 28026052
Nat Chem Biol. 2020 Feb;16(2):160-169
pubmed: 31819270
RNA. 2007 Mar;13(3):404-13
pubmed: 17242307
Oncogene. 2010 Feb 11;29(6):909-19
pubmed: 19935709