Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-50739
RNA 2015 Jul 01;217:1335-45. doi: 10.1261/rna.051565.115.
Show Gene links Show Anatomy links

Xenopus CAF1 requires NOT1-mediated interaction with 4E-T to repress translation in vivo.

Waghray S , Williams C , Coon JJ , Wickens M .


???displayArticle.abstract???
RNA-regulatory factors bound to 3' UTRs control translation and stability. Repression often is associated with poly(A) removal. The deadenylase CAF1 is a core component of the CCR4-NOT complex. Our prior studies established that CAF1 represses translation independent of deadenylation. We sought the mechanism of its deadenylation-independent repression in Xenopus oocytes. Our data reveal a chain of interacting proteins that links CAF1 to CCR4-NOT and to Xp54 and 4E-T. Association of CAF1 with NOT1, the major subunit of CCR4-NOT, is required for repression by CAF1 tethered to a reporter mRNA. Affinity purification-mass spectrometry and coimmunoprecipitation revealed that at least five members of the CCR4-NOT complex were recruited by CAF1. The recruitment of these proteins required NOT1, as did the ability of tethered CAF1 to repress translation. In turn, NOT1 was needed to recruit Xp54 and 4E-T. We examined the role of 4E-T in repression using mutations that disrupted either eIF4E-dependent or -independent mechanisms. Expression of a 4E-T truncation that still bound eIF4E alleviated repression by tethered CAF1, NOT1, and Xp54. In contrast, a mutant 4E-T that failed to bind eIF4E did not. Repression of global translation was affected only by the eIF4E-dependent mechanism. Reporters bearing IRES elements revealed that repression via tethered CAF1 and Xp54 is cap- and eIF4E-independent, but requires one or more of eIF4A, eIF4B, and eIF4G. We propose that RNA-binding proteins, and perhaps miRNAs, repress translation through an analogous chain of interactions that begin with the 3' UTR-bound repressor and end with the noncanonical activity of 4E-T.

???displayArticle.pubmedLink??? 26015597
???displayArticle.pmcLink??? PMC4478352
???displayArticle.link??? RNA
???displayArticle.grants??? [+]

Species referenced: Xenopus
Genes referenced: ccr4 cnot7 ddx6 eif4a1 eif4b eif4e eif4g1 not

References [+] :
Aslam, The Ccr4-NOT deadenylase subunits CNOT7 and CNOT8 have overlapping roles and modulate cell proliferation. 2009, Pubmed