دورية أكاديمية
tRNA m 1 G9 modification depends on substrate-specific RNA conformational changes induced by the methyltransferase Trm10.
| العنوان: | tRNA m 1 G9 modification depends on substrate-specific RNA conformational changes induced by the methyltransferase Trm10. |
|---|---|
| المؤلفون: | Strassler SE; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA; Graduate Program in Biochemistry, Cell and Developmental Biology, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia, USA., Bowles IE; Department of Chemistry and Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA; Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, USA., Krishnamohan A; Department of Chemistry and Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA; Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, USA., Kim H; Department of Chemistry and Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA., Edgington CB; Department of Chemistry and Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA., Kuiper EG; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA; Graduate Program in Biochemistry, Cell and Developmental Biology, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia, USA., Hancock CJ; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA., Comstock LR; Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina, USA., Jackman JE; Department of Chemistry and Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA; Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, USA. Electronic address: jackman.14@osu.edu., Conn GL; Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA; Graduate Program in Biochemistry, Cell and Developmental Biology, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia, USA. Electronic address: gconn@emory.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2023 Dec; Vol. 299 (12), pp. 105443. Date of Electronic Publication: 2023 Nov 08. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Nucleic Acid Conformation* , Nucleotides*/metabolism , RNA, Transfer*/chemistry , RNA, Transfer*/genetics , RNA, Transfer*/metabolism , Saccharomyces cerevisiae*/enzymology , Saccharomyces cerevisiae*/genetics , Saccharomyces cerevisiae*/metabolism , tRNA Methyltransferases*/chemistry , tRNA Methyltransferases*/metabolism, Humans ; Substrate Specificity |
| مستخلص: | 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. Competing Interests: 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. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Update of: bioRxiv. 2023 Oct 19:2023.02.01.526536. doi: 10.1101/2023.02.01.526536. (PMID: 36778341) |
| معلومات مُعتمدة: | R01 GM130135 United States GM NIGMS NIH HHS; S10 OD023582 United States OD NIH HHS |
| فهرسة مساهمة: | Keywords: RNA methylation; RNA structure; SHAPE RNA structure probing; SPOUT methyltransferase; substrate recognition; transfer RNA (tRNA) |
| المشرفين على المادة: | 0 (Nucleotides) 9014-25-9 (RNA, Transfer) EC 2.1.1.- (TRM10 protein, S cerevisiae) EC 2.1.1.- (TRMT10A protein, human) EC 2.1.1.- (tRNA Methyltransferases) |
| تواريخ الأحداث: | Date Created: 20231110 Date Completed: 20240129 Latest Revision: 20240624 |
| رمز التحديث: | 20240624 |
| مُعرف محوري في PubMed: | PMC10704376 |
| DOI: | 10.1016/j.jbc.2023.105443 |
| PMID: | 37949221 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
|---|---|
| DOI: | 10.1016/j.jbc.2023.105443 |