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Published on: June 12, 2018
Transient translational silencing by reversible mRNA deadenylation
J Huarte1, A Stutz, M L O'Connell
1Institute of Histology and Embryology, University of Geneva Medical School, Switzerland.
Abstract:
Tissue-type plasminogen activator (tPA) mRNA is stored, stable and untranslated, in the cytoplasm of fully grown primary mouse oocytes. Dormancy is associated with an unusually short poly(A) tail, and poly(A) tail elongation controls tPA mRNA translational activation during meiotic maturation. Here we show that the nuclear transcript of this mRNA is extensively polyadenylated and that primary oocytes contain a deadenylating activity capable of silencing the cytoplasmic message. The sequence determinants that control deadenylation and polyadenylation overlap; this AU-rich region thus serves as an adenylation control element (ACE). The translation of a reporter mRNA in primary oocytes is prevented upon inclusion of an ACE in its 3' untranslated region. Therefore, the stage-specific regulation of poly(A) tail length accounts for the regulated synthesis of tPA in oocytes, and reversible deadenylation provides a mechanism for the translational control of dormant mRNAs.
Insights
Messenger RNA (mRNA) translation in mouse oocytes is controlled by poly(A) tail length. Reversible deadenylation silences dormant mRNA, enabling regulated protein synthesis during maturation.
Area of Science:
- Molecular Biology
- Developmental Biology
- Gene Regulation
Background:
- Tissue-type plasminogen activator (tPA) mRNA is stored untranslated in primary mouse oocytes.
- Polyadenylation and deadenylation regulate mRNA translation during oocyte maturation.
- Short poly(A) tails are associated with mRNA dormancy.
Purpose of the Study:
- To investigate the mechanisms controlling tPA mRNA translational activation.
- To identify sequence elements regulating poly(A) tail length.
- To elucidate the role of deadenylation in translational control of dormant mRNAs.
Main Methods:
- Analysis of polyadenylation and deadenylation activities in oocytes.
- Identification of adenylation control elements (ACEs) in mRNA.
- Reporter mRNA translation assays in primary oocytes.
Main Results:
- Nuclear tPA mRNA transcripts are extensively polyadenylated.
- Oocytes possess a deadenylating activity that silences cytoplasmic mRNA.
- An AU-rich adenylation control element (ACE) in the 3' UTR prevents translation.
- Stage-specific poly(A) tail regulation controls tPA synthesis.
Conclusions:
- Reversible deadenylation is a key mechanism for translational control of dormant mRNAs.
- Poly(A) tail length regulation ensures stage-specific protein synthesis in oocytes.
- ACEs mediate translational silencing of untranslated mRNAs.
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