On-Enzyme Refolding Permits Small RNA and tRNA Surveillance by the CCA-Adding Enzyme

Kuhn, C. D., Wilusz, J. E., Zheng, Y., Beal, P. A., Joshua-Tor, L. (2015) On-Enzyme Refolding Permits Small RNA and tRNA Surveillance by the CCA-Adding Enzyme. Cell, 160 (4). pp. 644-658. ISSN 0092-8674

URL: http://www.ncbi.nlm.nih.gov/pubmed/25640237
DOI: 10.1016/j.cell.2015.01.005

Abstract

Transcription 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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > long non-coding RNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > sRNA
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL labs > Joshua-Tor lab
CSHL Cancer Center Shared Resources > Mass Spectrometry Service
CSHL Cancer Center Shared Resources > Proteomics Service
Depositing User: Matt Covey
Date Deposited: 09 Feb 2015 15:41
Last Modified: 30 Oct 2015 14:30
PMCID: PMC4329729
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31187

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