Title
CPEB3 and CPEB4 in neurons: analysis of RNA-binding specificity and translational control of AMPA receptor GluR2 mRNA
UMMS Affiliation
Graduate School of Biomedical Sciences; Program in Molecular Medicine
Publication Date
2006-10-07
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
CPEB is a sequence-specific RNA-binding protein that promotes polyadenylation-induced translation in oocytes and neurons. Vertebrates contain three additional genes that encode CPEB-like proteins, all of which are expressed in the brain. Here, we use SELEX, RNA structure probing, and RNA footprinting to show that CPEB and the CPEB-like proteins interact with different RNA sequences and thus constitute different classes of RNA-binding proteins. In transfected neurons, CPEB3 represses the translation of a reporter RNA in tethered function assays; in response to NMDA receptor activation, translation is stimulated. In contrast to CPEB, CPEB3-mediated translation is unlikely to involve cytoplasmic polyadenylation, as it requires neither the cis-acting AAUAAA nor the trans-acting cleavage and polyadenylation specificity factor, both of which are necessary for CPEB-induced polyadenylation. One target of CPEB3-mediated translation is GluR2 mRNA; not only does CPEB3 bind this RNA in vitro and in vivo, but an RNAi knockdown of CPEB3 in neurons results in elevated levels of GluR2 protein. These results indicate that CPEB3 is a sequence-specific translational regulatory protein.
DOI of Published Version
10.1038/sj.emboj.7601322
Source
EMBO J. 2006 Oct 18;25(20):4865-76. Epub 2006 Oct 5. Link to article on publisher's site
Journal/Book/Conference Title
The EMBO journal
Related Resources
PubMed ID
17024188
Repository Citation
Huang Y, Kan M, Lin C, Richter JD. (2006). CPEB3 and CPEB4 in neurons: analysis of RNA-binding specificity and translational control of AMPA receptor GluR2 mRNA. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1038/sj.emboj.7601322. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/555