Inefficient SRP interaction with a nascent chain triggers a mRNA quality control pathway.
Cell
; 156(1-2): 146-57, 2014 Jan 16.
Article
in En
| MEDLINE
| ID: mdl-24439374
ABSTRACT
Misfolded proteins are often cytotoxic, unless cellular systems prevent their accumulation. Data presented here uncover a mechanism by which defects in secretory proteins lead to a dramatic reduction in their mRNAs and protein expression. When mutant signal sequences fail to bind to the signal recognition particle (SRP) at the ribosome exit site, the nascent chain instead contacts Argonaute2 (Ago2), and the mutant mRNAs are specifically degraded. Severity of signal sequence mutations correlated with increased proximity of Ago2 to nascent chain and mRNA degradation. Ago2 knockdown inhibited degradation of the mutant mRNA, while overexpression of Ago2 or knockdown of SRP54 promoted degradation of secretory protein mRNA. The results reveal a previously unappreciated general mechanism of translational quality control, in which specific mRNA degradation preemptively regulates aberrant protein production (RAPP).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Biosynthesis
/
Protein Folding
/
Signal Recognition Particle
/
RNA Stability
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell
Year:
2014
Document type:
Article