Key result
Non-A residues in IVT mRNA poly(A) tails enhance translation efficiency and protein production versus pure tails.
Why the study?
Improving the translation efficiency of in vitro transcribed mRNA remains a core challenge for mRNA-based therapeutics and vaccines.
Does the inclusion of non-A residues in poly(A) tails improve mRNA translation efficiency in mouse and human cells?
Does the inclusion of non-A residues in poly(A) tails improve mRNA translation efficiency in mouse and human cells?
Answers are grounded in this paper and cite their sources.
The inclusion of non-A residues in mRNA poly(A) tails enhances translation efficiency, offering a novel approach to optimize mRNA-based therapeutics and vaccines.
SUMMARY In vitro transcribed (IVT) mRNA represents a new class of drug in both therapeutics and vaccines. Improving the translation efficiency of IVT mRNA remains a core challenge for mRNA-based applications. Here, using IVT mRNAs with poly(A) tails containing non-A residues which were recently revealed to be widespread in RNA poly(A) tails 1,2 , we unexpectedly find that non-A residues can effectively promote the mRNA translation. To further support our finding, we provide evidence that non-A residues associated with enhanced mRNA translation efficiency transcriptome-wide in mouse and human cells. Together, our study provides a novel approach to enhance mRNA translation efficiency by inclusion of non-A residues in the mRNA poly(A) tails, holding great potential to promote mRNA-based therapeutics and vaccines.
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Liu et al. (2021) studied this question. IVT mRNAs with poly(A) tails containing non-A residues vs. IVT mRNAs with pure A tails was evaluated on Translation efficiency (protein production). Inclusion of non-A residues in the poly(A) tails of in vitro transcribed mRNA significantly enhanced translation efficiency and protein production compared to pure poly(A) tails in human and mouse cells.
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