Abstract
Transcription in eukaryotes produces a number of long noncoding RNAs (lncRNAs). Two of these, MALAT1 and Menβ, 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 644-658 |
| Number of pages | 15 |
| Journal | Cell |
| Volume | 160 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 12 2015 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
On-enzyme refolding permits small RNA and tRNA surveillance by the CCA-adding enzyme. / Kuhn, Claus D.; Wilusz, Jeremy E.; Zheng, Yuxuan; Beal, Peter A.; Joshua-Tor, Leemor.
In: Cell, Vol. 160, No. 4, 12.02.2015, p. 644-658.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - On-enzyme refolding permits small RNA and tRNA surveillance by the CCA-adding enzyme
AU - Kuhn, Claus D.
AU - Wilusz, Jeremy E.
AU - Zheng, Yuxuan
AU - Beal, Peter A.
AU - Joshua-Tor, Leemor
PY - 2015/2/12
Y1 - 2015/2/12
N2 - Transcription in eukaryotes produces a number of long noncoding RNAs (lncRNAs). Two of these, MALAT1 and Menβ, 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.
AB - Transcription in eukaryotes produces a number of long noncoding RNAs (lncRNAs). Two of these, MALAT1 and Menβ, 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.
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U2 - 10.1016/j.cell.2015.01.005
DO - 10.1016/j.cell.2015.01.005
M3 - Article
VL - 160
SP - 644
EP - 658
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -