tRNA m
RNA methylation
RNA structure
SHAPE RNA structure probing
SPOUT methyltransferase
substrate recognition
transfer RNA (tRNA)
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
08 Nov 2023
08 Nov 2023
Historique:
received:
01
02
2023
revised:
19
10
2023
accepted:
06
11
2023
pubmed:
11
11
2023
medline:
11
11
2023
entrez:
10
11
2023
Statut:
aheadofprint
Résumé
The methyltransferase Trm10 modifies a subset of tRNAs on the base N1 position of the ninth nucleotide in the tRNA core. Trm10 is conserved throughout Eukarya and Archaea, and mutations in the human gene (TRMT10A) have been linked to neurological disorders such as microcephaly and intellectual disability, as well as defects in glucose metabolism. Of the 26 tRNAs in yeast with guanosine at position 9, only 13 are substrates for Trm10. However, no common sequence or other posttranscriptional modifications have been identified among these substrates, suggesting the presence of some other tRNA feature(s) that allow Trm10 to distinguish substrate from nonsubstrate tRNAs. Here, we show that substrate recognition by Saccharomyces cerevisiae Trm10 is dependent on both intrinsic tRNA flexibility and the ability of the enzyme to induce specific tRNA conformational changes upon binding. Using the sensitive RNA structure-probing method SHAPE, conformational changes upon binding to Trm10 in tRNA substrates, but not nonsubstrates, were identified and mapped onto a model of Trm10-bound tRNA. These changes may play an important role in substrate recognition by allowing Trm10 to gain access to the target nucleotide. Our results highlight a novel mechanism of substrate recognition by a conserved tRNA modifying enzyme. Further, these studies reveal a strategy for substrate recognition that may be broadly employed by tRNA-modifying enzymes which must distinguish between structurally similar tRNA species.
Identifiants
pubmed: 37949221
pii: S0021-9258(23)02471-7
doi: 10.1016/j.jbc.2023.105443
pmc: PMC10704376
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105443Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM130135
Pays : United States
Organisme : NIH HHS
ID : S10 OD023582
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Nat Protoc. 2006;1(3):1610-6
pubmed: 17406453
Bioorg Med Chem. 2015 Aug 1;23(15):5050-5055
pubmed: 26037613
Mol Cell. 2011 Feb 4;41(3):331-42
pubmed: 21292165
PLoS Genet. 2013 Oct;9(10):e1003888
pubmed: 24204302
Methods. 2010 Oct;52(2):150-8
pubmed: 20554050
Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2304128120
pubmed: 37307464
ACS Catal. 2020 Aug 7;10(15):8058-8068
pubmed: 32904895
Chem Biol. 2014 Feb 20;21(2):174-85
pubmed: 24315934
EMBO J. 1997 Mar 3;16(5):1122-34
pubmed: 9118950
F1000Res. 2015 Sep 28;4:912
pubmed: 26535115
Science. 1989 May 26;244(4907):986-9
pubmed: 2471265
Genes Dev. 2010 Sep 1;24(17):1832-60
pubmed: 20810645
Chembiochem. 2006 Feb;7(2):243-5
pubmed: 16365907
J Biol Chem. 2014 Sep 19;289(38):26189-26200
pubmed: 25086036
RNA. 2005 Jul;11(7):1051-63
pubmed: 15987815
Biochemistry. 1997 Jul 22;36(29):8699-709
pubmed: 9220956
BMC Bioinformatics. 2003 Mar 14;4:9
pubmed: 12689347
RNA. 2017 Feb;23(2):240-249
pubmed: 27821510
Nucleic Acids Res. 2018 Nov 2;46(19):10302-10318
pubmed: 30247717
Science. 1999 May 14;284(5417):1171-4
pubmed: 10325228
Nat Struct Mol Biol. 2021 Sep;28(9):713-723
pubmed: 34489609
Trends Biochem Sci. 2003 Jun;28(6):329-35
pubmed: 12826405
Nucleic Acids Res. 2012 Dec;40(22):11583-93
pubmed: 23042678
Nucleic Acids Res. 2009 Jan;37(Database issue):D159-62
pubmed: 18957446
Chem Biol. 2014 Oct 23;21(10):1351-1360
pubmed: 25219964
Nucleic Acids Res. 2021 Nov 18;49(20):11810-11822
pubmed: 34718722
RNA. 2019 Oct;25(10):1366-1376
pubmed: 31292261
Enzymes. 2017;41:51-88
pubmed: 28601226
RNA. 2003 May;9(5):574-85
pubmed: 12702816
Nucleic Acids Res. 2013 Jan;41(Database issue):D262-7
pubmed: 23118484
Biochemistry. 1993 Apr 20;32(15):3836-41
pubmed: 8385989
Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120352119
pubmed: 35357969
J Biol Chem. 2019 Nov 15;294(46):17642-17653
pubmed: 31594862
J Biochem. 1990 Mar;107(3):331-8
pubmed: 2187856
BMC Bioinformatics. 2007 Mar 05;8:73
pubmed: 17338813
RNA. 2008 Apr;14(4):666-74
pubmed: 18314501
RNA. 2018 Oct;24(10):1277-1284
pubmed: 30026310
Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):E4197-205
pubmed: 26183229
Nucleic Acids Res. 2016 Jan 29;44(2):940-53
pubmed: 26673726
Nucleic Acids Res. 2017 Sep 6;45(15):9019-9029
pubmed: 28911116
Nucleic Acids Res. 2011 Mar;39(6):2445-57
pubmed: 21087996
J Med Genet. 2014 Sep;51(9):581-6
pubmed: 25053765
Methods Mol Biol. 2012;941:157-69
pubmed: 23065560
RNA. 2014 Aug;20(8):1257-71
pubmed: 24951554
RNA. 2013 Aug;19(8):1137-46
pubmed: 23793893
Biochemistry. 2010 Jun 22;49(24):4934-44
pubmed: 20459084
J Mol Microbiol Biotechnol. 2002 Jan;4(1):71-5
pubmed: 11763972
J Biochem. 1989 Nov;106(5):798-802
pubmed: 2482290
Nucleic Acids Res. 2020 Jun 19;48(11):6157-6169
pubmed: 32392304
J Biol Chem. 2022 Oct;298(10):102393
pubmed: 35988649
Cell. 1994 Jan 28;76(2):357-69
pubmed: 8293469
J Am Chem Soc. 2005 Mar 30;127(12):4223-31
pubmed: 15783204
Am J Med Genet A. 2015 Dec;167A(12):3167-73
pubmed: 26297882
Nucleic Acids Res. 2014 Jan;42(1):509-25
pubmed: 24081582
RNA Biol. 2017 Feb;14(2):156-163
pubmed: 27937535
Diabet Med. 2016 Sep;33(9):e21-5
pubmed: 26526202
Methods Mol Biol. 2012;941:43-58
pubmed: 23065552
Methods Enzymol. 2014;549:165-87
pubmed: 25432749
Nucleic Acids Res. 2015 Sep 3;43(15):7489-503
pubmed: 26202969