Change search
ReferencesLink to record
Permanent link

Direct link
Inefficient SRP Interaction with a Nascent Chain Triggers a mRNA Quality Control Pathway
Show others and affiliations
2014 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 156, no 1-2, 146-157 p.Article in journal (Refereed) Published
Abstract [en]

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 mechanismof translational quality control, in which specific mRNA degradation preemptively regulates aberrant protein production (RAPP).

Place, publisher, year, edition, pages
2014. Vol. 156, no 1-2, 146-157 p.
National Category
Biochemistry and Molecular Biology Cell Biology
URN: urn:nbn:se:su:diva-100858DOI: 10.1016/j.cell.2013.12.017ISI: 000329912200017OAI: diva2:698225


Available from: 2014-02-20 Created: 2014-02-17 Last updated: 2014-02-20Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Nilsson, IngMarievon Heijne, Gunnar
By organisation
Department of Biochemistry and BiophysicsScience for Life Laboratory (SciLifeLab)
In the same journal
Biochemistry and Molecular BiologyCell Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 23 hits
ReferencesLink to record
Permanent link

Direct link