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Poly(A)-tail-promoted translation in yeast: implications for translational control
T Preiss1, M Muckenthaler, M W Hentze
1Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Summary
The mRNA cap structure and poly(A) tail work together for translation. The poly(A) tail can independently recruit ribosomes, but mRNA competition restores full translational control by both elements.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The cap structure and poly(A) tail synergistically enhance mRNA translation.
- The poly(A) tail can independently promote ribosome recruitment to internal initiation sites.
Purpose of the Study:
- Investigate how regulatory elements in the 5' untranslated region (5' UTR) function with the poly(A) tail.
- Determine how regulated polyadenylation supports protein synthesis.
- Understand the interplay between cap-dependent and poly(A)-tail-dependent translation.
Main Methods:
- Utilized reporter mRNAs with regulatory upstream open reading frames (uORFs) and iron-responsive elements (IRES) in the 5' UTR.
- Employed yeast spheroplasts and cell-free translation systems.
- Assessed translation efficiency under competitive and non-competitive conditions with varying poly(A) tail lengths.
Main Results:
- The poly(A) tail bypasses cap-dependent translation blocks caused by uORFs and repressor proteins under non-competitive conditions.
- mRNA competition reinstates translational control by 5' UTR elements when both cap and poly(A) tail are present.
- Poly(A) tail elongation enhances translational efficiency, especially under competitive conditions.
Conclusions:
- The poly(A) tail's role in translation is context-dependent, influenced by competition and other regulatory elements.
- Synergistic action of the cap and poly(A) tail is crucial for robust translational control.
- Findings provide insights into regulated polyadenylation and its impact on protein synthesis.