Transient translational silencing by reversible mRNA deadenylation

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.