The nuclear experience of CPEB: implications for RNA processing and translational control.
CPEB is a sequence-specific RNA binding protein that promotes polyadenylation-induced translation in early development, during cell cycle progression and cellular senescence, and following neuronal synapse stimulation. It controls polyadenylation and translation through other interacting molecules, most notably the poly(A) polymerase Gld2, the deadenylating enzyme PARN, and the eIF4E-binding protein Maskin. Here, we report that CPEB shuttles between the nucleus and cytoplasm and that its export occurs via the CRM1-dependent pathway. In the nucleus of Xenopus oocytes, CPEB associates with lampbrush chromosomes and several proteins involved in nuclear RNA processing. CPEB also interacts with Maskin in the nucleus as well as with CPE-containing mRNAs. Although the CPE does not regulate mRNA export, it influences the degree to which mRNAs are translationally repressed in the cytoplasm. Moreover, CPEB directly or indirectly mediates the alternative splicing of at least one pre-mRNA in mouse embryo fibroblasts as well as certain mouse tissues. We propose that CPEB, together with Maskin, binds mRNA in the nucleus to ensure tight translational repression upon export to the cytoplasm. In addition, we propose that nuclear CPEB regulates specific pre-mRNA alternative splicing.
PubMed ID: 20040591
PMC ID: PMC2811663
Article link: RNA.
Grant support: DK32520 NIDDK NIH HHS , F32 CA12496 NCI NIH HHS , GM46779 NIGMS NIH HHS , HD37267 NICHD NIH HHS , HG004634 NHGRI NIH HHS , R01 GM046779 NIGMS NIH HHS
Genes referenced: cpeb1 eif4e papd4 parn tacc3 xpo1