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PreprintCited by 11RNA and protein synthesis mechanismsRNA Research and SplicingRNA Interference and Gene Delivery

Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails

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Liu, Yusheng, Nie, Hu, Sun, Rongrong, Wang, Jiaqiang, Lu, Falong·2021·Science China Life Sciences
DOI 10.1101/2021.08.30.458298
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Abstract

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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  • The study by Liu et al. did not evaluate stability of templates nor translation efficiency in human primary cells or in vivo.

    “This study did not evaluate stability of templates nor translation efficiency in human primary cells or in vivo.”

    From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [22]

    The cell-culture and transfection Methods describe translation experiments in HeLa cells, not human primary cells, and the paper does not report an in vivo test of the engineered mRNAs. But the 'Non-A residues promote translation efficiency of IVT mRNA' section uses qPCR to assess whether increased protein production reflects mRNA stability, while the 'non-A residues are associated with high translation efficiency in vivo' section analyzes translation efficiency of endogenous mRNAs in mouse oocytes. The blanket statement that the study did not evaluate template stability or translation efficiency in vivo is therefore too broad. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Guanylation stabilizes mRNA by reducing deadenylation, and cellular mRNAs with non-A tails are highly translated.

    “Furthermore, guanylation has been reported to stabilize mRNA by reducing deadenylation20,22 and that cellular mRNAs with non-A tails are highly translated.22”

    From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [22]

  • mRNA tails containing C and G residues were more efficiently translated than mRNA with pure A tails in HeLa cells.

    “A recent study by Liu et al. reported that mRNA tails containing C ang G residues were more efficiently translated than mRNA with pure A tails in HeLa cells.22”

    From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [22]

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Cited by

Sorted by citations

Authors
Liu, Y., Nie, H., Sun, R., Wang, J., & Lu, F.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Northeast Agricultural University (CN)
Corresponding author
  • Liu, Yusheng
  • Wang, Jiaqiang
  • Lu, Falong
ORCID
Venue
Science China Life Sciences
Publisher
openRxiv
Published
2021-08-31
Volume
68
Issue
12
Pages
3506-3508
ISSN
1674-7305 (ISSN-L)
DOI
10.1101/2021.08.30.458298
OpenAlex
W4414622638
Cited by
11
References
3
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 3
FWCI
1.38
Type
journal article
Language
en
Open access
Locations
  • Science China Life Sciences (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (31970588)
  • Chinese Academy of Sciences (XDA24020203)
  • China Postdoctoral Science Foundation (2020M670516, 2020T130687, 2020T130687, 2020M670516)
  • Natural Science Foundation of Heilongjiang Province (YQ2020C003)
  • National Key Research and Development Program of China (2018YFA0107001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
in vitro transcription, mRNA translation efficiency, poly(A) tail, mRNA 3' end, poly(A) polymerase, translation efficiency

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