A combinatorial code for CPE-mediated translational control.
Cytoplasmic polyadenylation plays a key role in the translational control of mRNAs driving biological processes such as gametogenesis, cell-cycle progression, and synaptic plasticity. What determines the distinct time of polyadenylation and extent of translational control of a given mRNA, however, is poorly understood. The polyadenylation-regulated translation is controlled by the cytoplasmic polyadenylation element (CPE) and its binding protein, CPEB, which can assemble both translational repression or activation complexes. Using a combination of mutagenesis and experimental validation of genome-wide computational predictions, we show that the number and relative position of two elements, the CPE and the Pumilio-binding element, with respect to the polyadenylation signal define a combinatorial code that determines whether an mRNA will be translationally repressed by CPEB, as well as the extent and time of cytoplasmic polyadenylation-dependent translational activation.
Piqué
Maria
M
Centre for Genomic Regulation (CRG), UPF, C/Dr. Aiguader, 88, 08003 Barcelona, Spain.
López
José Manuel
JM
Foissac
Sylvain
S
Guigó
Roderic
R
Méndez
Raúl
R
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008540:Meiosis; D051379:Mice; D016296:Mutagenesis; D009865:Oocytes / Q000378:metabolism; D026723:Polyadenylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology; D014176:Protein Biosynthesis; D039104:RNA 3' Polyadenylation Signals; D023121:RNA, Messenger, Stored / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism
D020413:3' Untranslated Regions; C490388:Cpeb1 protein, Xenopus; D019926:Cyclin B; C430875:PUM1 protein, Xenopus; D023121:RNA, Messenger, Stored; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D011374:Progesterone