The impact of mRNA poly(A) tail length on eukaryotic translation stages

Nikita Biziaev1, Alexey Shuvalov1,2, Ali Salman1

  • 1Engelhardt Institute of Molecular Biology, the Russian Academy of Sciences, 119991 Moscow, Russia.

PubMed

Insights

The poly(A) tail influences human mRNA translation. While cap-dependent translation is mostly independent of tail length, cap-independent translation increases with poly(A) tail length, suggesting a role in translation regulation.

Area of Science:

  • Molecular Biology
  • Gene Expression Regulation

Background:

  • The poly(A) tail is crucial for mRNA stability and translation via Poly(A)-Binding Protein (PABP).
  • The precise impact of poly(A) tail length on human mRNA translation efficiency is not fully elucidated.

Purpose of the Study:

  • To investigate the effect of varying poly(A) tail lengths on human mRNA translation rates.
  • To understand how poly(A) tail length influences cap-dependent and cap-independent translation.

Main Methods:

  • In vitro translation assays using cell lysates with engineered mRNAs possessing distinct poly(A) tail lengths.
  • Analysis of translation initiation and termination stages.

Main Results:

  • Cap-dependent translation is enhanced by the poly(A) tail but largely insensitive to its length, except for a 75 nt tail.
  • Cap-independent translation shows a positive correlation with poly(A) tail length.
  • Poly(A) tail presence affects initiation and termination, but not initiation efficiency; longer tails enhance peptidyl-tRNA hydrolysis via eRFs.

Conclusions:

  • A 75 nt poly(A) tail may be critical for forming a double closed-loop structure in human mRNA.
  • This structure likely couples translation initiation and termination, impacting overall translation efficiency.

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