Mixed tailing by TENT4A and TENT4B shields mRNA from rapid deadenylation
Abstract
A tale of not-so-pure tails: The poly(A) tail of mRNA has been thought to be a pure stretch of adenosine nucleotides with little informational content except for length. Lim et al. identified enzymes that can decorate poly(A) tails with non-A nucleotides. The noncanonical poly(A) polymerases, TENT4A and TENT4B, incorporate intermittent non-A residues (G, U, or C) with a preference for guanosine, which results in a heterogenous poly(A) tail. Deadenylases trim poly(A) tails to initiate mRNA degradation but stall at the non-A residues. In effect, the not-so-pure tail stabilizes mRNAs by slowing down deadenylation. Science , this issue p. 701
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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 [20]
Guanosine residues are the most frequent non-adenosine nucleotides in poly(A) tails in humans and other species.
“Guanosine residues are the most frequent non-adenosine nucleotides in poly(A) tails in humans and other species.20,21”
From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [20]
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- Authors
- Lim, J., Kim, D., Lee, Y.-S., Ha, M., Lee, M., Yeo, J., Chang, H., Song, J., Ahn, K., & Kim, V. N.
- Affiliations
- Seoul National University (KR)
- Center for RNA Research, Institute for Basic Science, Seoul 151-742, Republic of Korea.
- Corresponding author
- Lim, Jaechul
- Lee, Young-suk
- Kim, V. Narry
- ORCID
- Venue
- Science
- Published
- 2018-08-17
- Volume
- 361
- Issue
- 6403
- Pages
- 701-704
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2884627335
- Cited by
- 165
- References
- 0
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 30 · 2023: 19 · 2022: 16 · 2021: 16 · 2020: 18 · 2019: 15 · 2018: 9
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- mRNA deadenylation, CCR4-NOT complex, mRNA degradation, mRNA half-life, post-transcriptional regulation, poly(A) tail
- MeSH terms
- Chromosomal Proteins, Non-Histone, DNA-Directed DNA Polymerase, Exoribonucleases, Fibroblasts, Gene Expression Regulation, HeLa Cells, Humans, RNA Nucleotidyltransferases, RNA, Messenger, Gene Deletion, RNA 3' End Processing, Gene Knockout Techniques, HEK293 Cells
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