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A combinatorial code for mRNA 3'-UTR-mediated translational control in the mouse oocyte
Xing-Xing Dai1, Jun-Chao Jiang1, Qian-Qian Sha1
1MOEKey Laboratory for Biosystems Homeostasis & Protection and InnovationCenter for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Abstract:
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, Btg4 and 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.
Insights
Maternal mRNA translation during oocyte maturation is controlled by a code within 3' untranslated regions. This code dictates when genes are turned on or off, ensuring proper development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Meiotic maturation in mammalian oocytes requires precise control of maternal mRNA translation.
- Cytoplasmic polyadenylation, influenced by the polyadenylation signal (PAS) and cytoplasmic polyadenylation element (CPE), is crucial for this regulation.
- Understanding the cis-element code governing mRNA translation is vital for comprehending oocyte development.
Purpose of the Study:
- To decipher the combinatorial code within 3'-UTRs that regulates developmental stage-specific mRNA translation during meiotic maturation.
- To investigate the roles of PAS and CPE positioning in controlling translational repression and activation.
Main Methods:
- Analysis of the 3'-UTRs of mouse Cpeb1, Btg4, and Cnot6l mRNAs.
- Investigating the relationship between PAS and CPE elements and their impact on translation at different meiotic stages.
Main Results:
- Translation at the germinal vesicle (GV) stage requires PAS elements distant from CPEs.
- PAS elements near the 3'-end are effective for GV translation if not close to CPEs.
- Translational repression (GV stage) and activation (post-germinal vesicle breakdown) depend on CPEs adjacent to PAS.
- The number and position of CPEs relative to PAS influence translational repression efficiency in GV oocytes.
Conclusions:
- A novel mechanism involving proximal PAS elements mediating 3'-terminal polyadenylation and translation of maternal transcripts has been identified.
- The positioning and number of CPEs and PASs form a combinatorial code that precisely regulates maternal mRNA translation during oocyte maturation.
- This regulatory code is essential for the temporal and spatial control of gene expression during mammalian oogenesis.