Dear Editor,Transfer RNA(tRNA)is an indispensable adaptor molecule in the messenger RNA(mRNA)translation machinery,facilitating the conversion of genetic information encoded in mRNA into functional proteins.Numerous p...Dear Editor,Transfer RNA(tRNA)is an indispensable adaptor molecule in the messenger RNA(mRNA)translation machinery,facilitating the conversion of genetic information encoded in mRNA into functional proteins.Numerous posttranscriptional modifications in tRNA have been identified,which play significantroles in modulating tRNA folding,biochemical stability,amino-acylation,and codon–anticodon interaction(Suzuki,2021).TRMT10A,the mammalian homolog of Trm10,incorporates N1-methylguanosine modification at position 9(m1G9)of various cytoplasmic tRNAs,including tRNAGln and tRNAIniMeth(Vilardo et al.,2020).Mutations in human TRMT10A,which is enriched in pancreatic islets and brain(Igoillo-Esteve et al.,2013),are often associated with microcephaly,intellectual disability,early-onset diabetes,and short stature(Igoillo-Esteve et al.,2013;Uçan Tokuçet al.,2024).展开更多
The ubiquitin-related modifier Urm1 can be covalently conjugated to lysine residues of other proteins,such as yeast Ahp1 and human MOCS3,through a mechanism involving the E1-like protein Uba4(MOCS3 in humans).Similar ...The ubiquitin-related modifier Urm1 can be covalently conjugated to lysine residues of other proteins,such as yeast Ahp1 and human MOCS3,through a mechanism involving the E1-like protein Uba4(MOCS3 in humans).Similar to ubiquitination,urmylation requires a thioester intermediate and forms isopeptide bonds between Urm1 and its substrates.In addition,the urmylation process can be significantly enhanced by oxidative stress.Recent findings have demonstrated that Urm1 also acts as a sulfur carrier in the thiolation of eukaryotic tRNA via a mechanism that requires the formation of a thiocarboxylated Urm1.This role is very similar to that of prokaryotic sulfur carriers such as MoaD and ThiS.Evidence strongly supports the hypothesis that Urm1 is the molecular fossil in the evolutionary link between prokaryotic sulfur carriers and eukaryotic ubiquitin-like proteins.In the present review,we discuss the dual role of Urm1 in protein and tRNA modification.展开更多
基金Supplementary material is available at Journal of Molecular Cell Biology online.This study was supported by grants from the National Natural Science Foundation of China(82230075 to D.G.32270159 to J.W.)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2023A1515012613 to J.W.)Shenzhen Science and Technology Program(JCYJ20200109142201695 and KQTD20180411143323605 to D.G.,JCYJ20220530145608018 to J.W.)Shenzhen Key Laboratory of Systems Medicine for Inflammatory Diseases(ZDSYS20220606100803007 to J.W.).
文摘Dear Editor,Transfer RNA(tRNA)is an indispensable adaptor molecule in the messenger RNA(mRNA)translation machinery,facilitating the conversion of genetic information encoded in mRNA into functional proteins.Numerous posttranscriptional modifications in tRNA have been identified,which play significantroles in modulating tRNA folding,biochemical stability,amino-acylation,and codon–anticodon interaction(Suzuki,2021).TRMT10A,the mammalian homolog of Trm10,incorporates N1-methylguanosine modification at position 9(m1G9)of various cytoplasmic tRNAs,including tRNAGln and tRNAIniMeth(Vilardo et al.,2020).Mutations in human TRMT10A,which is enriched in pancreatic islets and brain(Igoillo-Esteve et al.,2013),are often associated with microcephaly,intellectual disability,early-onset diabetes,and short stature(Igoillo-Esteve et al.,2013;Uçan Tokuçet al.,2024).
文摘The ubiquitin-related modifier Urm1 can be covalently conjugated to lysine residues of other proteins,such as yeast Ahp1 and human MOCS3,through a mechanism involving the E1-like protein Uba4(MOCS3 in humans).Similar to ubiquitination,urmylation requires a thioester intermediate and forms isopeptide bonds between Urm1 and its substrates.In addition,the urmylation process can be significantly enhanced by oxidative stress.Recent findings have demonstrated that Urm1 also acts as a sulfur carrier in the thiolation of eukaryotic tRNA via a mechanism that requires the formation of a thiocarboxylated Urm1.This role is very similar to that of prokaryotic sulfur carriers such as MoaD and ThiS.Evidence strongly supports the hypothesis that Urm1 is the molecular fossil in the evolutionary link between prokaryotic sulfur carriers and eukaryotic ubiquitin-like proteins.In the present review,we discuss the dual role of Urm1 in protein and tRNA modification.
