Biochemical and structural insights into a 5' to 3' RNA ligase reveal a potential role in tRNA ligation

• 成果类型: Article
• 署名作者: Hu, Yingjie; Lopez, Victor A.; Xu, Hengyi; Pfister, James P.; Song, Bing; Servage, Kelly A.; Sakurai, Masahiro; Jones, Benjamin T.; Mendell, Joshua T.; Wang, Tao; Wu, Jun; Lambowitz, Alan M.; Tomchick, Diana R.; Pawlowski, Krzysztof; Tagliabracci, Vincent S.
• 署名单位: University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11814
• DOI: 10.1073/pnas.24082491211
• 发表日期: 2024-10-15
• 关键词: mechanism; biology; 2-metal; kinase; FAMILY; enzyme

摘要

ATP- grasp superfamily enzymes contain a hand- like ATP- binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here, we identify C12orf29 (RLIG1) as an atypical ATP- grasp enzyme that ligates RNA. Human RLIG1 and its homologs autoadenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5'- phosphate and a 3'- hydroxyl. RLIG1 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Transcriptomic analyses of Rlig1 knockout mice revealed significant alterations in global tRNA levels in the brains of female mice, but not in those of male mice. Furthermore, crystal structures of a RLIG1 homolog from Yasminevirus bound to nucleotides revealed a minimal and atypical RNA ligase fold with a conserved active site architecture that participates in catalysis. Collectively, our results identify RLIG1 as an RNA ligase and suggest its involvement in tRNA biology.