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Tales of poly(A): a review
1Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
Abstract:
Until recently, evidence to support a translational role for the 3'-poly(A) tract of eukaryotic mRNAs has been mostly indirect, including: a correlation between the adenylation status of individual mRNAs and their translatability in vivo or in vitro, the demonstration that exogenously added poly(A) is a potent competitive inhibitor of the translation of poly(A)+mRNA, but not poly(A)-mRNAs in vitro, and a correlation between the abundance and stability of poly(A)-binding proteins (PABPs) and the rate of translational initiation in vivo. However, more recent studies demonstrate directly that poly(A)+mRNAs can initiate translation more efficiently than poly(A)-mRNAs, and indicate that this effect is: (i) targeted to the formation of 80S initiation complexes, and (ii) likely to be mediated by the cytoplasmic PABP. We suggest that the 3'-poly(A) tail should be considered a translational enhancer which may stimulate translational initiation in much the same way that transcriptional enhancers are thought to stimulate transcriptional initiation.
Insights
The 3'-poly(A) tail of eukaryotic messenger RNAs (mRNAs) acts as a translational enhancer. It directly promotes the efficient formation of 80S initiation complexes, likely via cytoplasmic poly(A)-binding proteins (PABPs).
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The translational role of the 3'-poly(A) tract in eukaryotic mRNAs was previously supported by indirect evidence.
- Previous studies showed correlations between mRNA adenylation status and translatability, inhibition by exogenous poly(A), and links between poly(A)-binding proteins (PABPs) and translational initiation rates.
Purpose of the Study:
- To provide direct evidence for the translational role of the 3'-poly(A) tail.
- To elucidate the mechanism by which the 3'-poly(A) tail influences mRNA translation.
Main Methods:
- Directly comparing the translation efficiency of poly(A)+mRNAs and poly(A)-mRNAs.
- Investigating the specific stage of translation affected by the poly(A) tail.
- Assessing the involvement of cytoplasmic poly(A)-binding proteins (PABPs).
Main Results:
- Polyadenylated mRNAs (poly(A)+mRNAs) initiate translation more efficiently than non-polyadenylated mRNAs (poly(A)-mRNAs).
- This enhanced translation is specifically targeted to the formation of 80S initiation complexes.
- The effect is likely mediated by cytoplasmic PABPs.
Conclusions:
- The 3'-poly(A) tail functions as a direct translational enhancer for eukaryotic mRNAs.
- This enhancement mechanism involves promoting 80S initiation complex formation, potentially through PABP interaction.
- The poly(A) tail's role in translation initiation is analogous to the function of transcriptional enhancers in gene expression.