4x4w | pdb_00004x4w
Crystal structure of the full-length human mitochondrial CCA-adding enzyme
Structural highlights
FunctionTRNT1_HUMAN Isoform 1: Adds and repairs the conserved 3'-CCA sequence necessary for the attachment of amino acids to the 3' terminus of tRNA molecules, using CTP and ATP as substrates.[1] Isoform 2: Adds 2 C residues (CC-) to the 3' terminus of tRNA molecules instead of a complete CCA end as isoform 1 does (in vitro).[2] Publication Abstract from PubMedTranscription in eukaryotes produces a number of long noncoding RNAs (lncRNAs). Two of these, MALAT1 and Menbeta, generate a tRNA-like small RNA in addition to the mature lncRNA. The stability of these tRNA-like small RNAs and bona fide tRNAs is monitored by the CCA-adding enzyme. Whereas CCA is added to stable tRNAs and tRNA-like transcripts, a second CCA repeat is added to certain unstable transcripts to initiate their degradation. Here, we characterize how these two scenarios are distinguished. Following the first CCA addition cycle, nucleotide binding to the active site triggers a clockwise screw motion, producing torque on the RNA. This ejects stable RNAs, whereas unstable RNAs are refolded while bound to the enzyme and subjected to a second CCA catalytic cycle. Intriguingly, with the CCA-adding enzyme acting as a molecular vise, the RNAs proofread themselves through differential responses to its interrogation between stable and unstable substrates. On-Enzyme Refolding Permits Small RNA and tRNA Surveillance by the CCA-Adding Enzyme.,Kuhn CD, Wilusz JE, Zheng Y, Beal PA, Joshua-Tor L Cell. 2015 Feb 12;160(4):644-58. doi: 10.1016/j.cell.2015.01.005. Epub 2015 Jan, 29. PMID:25640237[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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