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Updated: May 27, 2026

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC
Published on: May 9, 2020
tRNAs marked with CCACCA are targeted for degradation
Jeremy E Wilusz1, Joseph M Whipple, Eric M Phizicky
1Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. wilusz@mit.edu
The CCA-adding enzyme marks unstable transfer RNAs (tRNAs) for degradation by adding CCACCA instead of CCA. This process, observed across all life kingdoms, helps control tRNA levels and prevent translation errors.
Area of Science:
- Molecular Biology
- RNA Biology
- Biochemistry
Background:
- Transfer RNAs (tRNAs) are essential for protein synthesis.
- The CCA-adding enzyme (ATP(CTP):tRNA nucleotidyltransferase) typically adds CCA to tRNA 3' ends.
- This CCA addition is crucial for tRNA function and amino acid attachment.
Purpose of the Study:
- To investigate the role of the CCA-adding enzyme in tRNA quality control.
- To determine the mechanism by which unstable tRNAs are regulated.
- To explore the universality of CCA-adding enzyme function across different life forms.
Main Methods:
- Comparative analysis of CCA-adding enzyme activity in vitro.
- In vivo studies using model organisms.
- RNA sequencing and analysis of modified tRNAs.
Main Results:
- CCA-adding enzymes selectively mark structurally unstable tRNAs and tRNA-like small RNAs for degradation.
- Instead of CCA, these enzymes add a CCACCA sequence to the 3' ends of targeted RNAs.
- Hypomodified mature tRNAs also undergo CCACCA addition, indicating a rapid tRNA decay pathway.
Conclusions:
- The CCA-adding enzyme functions as a critical component of tRNA quality control.
- CCACCA addition serves as a universal mechanism for regulating tRNA abundance.
- This pathway likely prevents errors during protein translation by eliminating faulty tRNAs.
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