A combinatorial code for mRNA 3-UTR-mediated translational control in the mouse oocyte

作者：Dai, Xing-Xing; Jiang, Jun-Chao; Sha, Qian-Qian; Jiang, Yu; Ou, Xiang-Hong; Fan, Heng-Yu^*

来源：Nucleic Acids Research, 2019, 47(1): 328-340.

DOI：10.1093/nar/gky971

• TO-ZYGOTIC TRANSITION
• CYTOPLASMIC POLYADENYLATION
• MEIOTIC MATURATION
• BINDING PROTEINS
• DEGRADATION
• CPEB
• TRANSCRIPTOME
• PROGRESSION
• ACTIVATION
• CLEARANCE

Meiotic maturation of mammalian oocytes depends on the temporally and spatially regulated cytoplasmic polyadenylation and translational activation of maternal mRNAs. Cytoplasmic polyadenylation is controlled by cis-elements in the 3-UTRs of mRNAs including the polyadenylation signal (PAS), which is bound by the cleavage and polyadenylation specificity factor (CPSF)and the cytoplasmic polyadenylation element (CPE), which recruits CPE binding proteins. Using the 3-UTRs of mouse Cpeb1, Btg4and Cnot6l mRNAs, we deciphered the combinatorial code that controls developmental stage-specific translation during meiotic maturation: (i) translation of a maternal transcript at the germinal vesicle (GV) stage requires one or more PASs that locate far away from CPEs; (ii) PASs distal and proximal to the 3-end of the transcripts are equally effective in mediating translation at the GV stage, as long as they are not close to the CPEs; (iii) Both translational repression at the GV stage and activation after germinal vesicle breakdown require at least one CPE adjacent to the PAS; (iv) The numbers and positions of CPEs in relation to PASs within the 3-UTR of a given transcript determines its repression efficiency in GV oocytes. This study reveals a previously unrecognized non-canonical mechanism by which the proximal PASs mediate 3-terminal polyadenylation and translation of maternal transcripts.

• 出版日期2019-1-10
• 单位浙江大学