Recognition of Poly(A) RNA through Its Intrinsic Helical Structure
Open accessAbstract
The polyadenosine (poly(A)) tail, which is found on the 3' end of almost all eukaryotic messenger RNAs (mRNAs), plays an important role in the posttranscriptional regulation of gene expression. Shortening of the poly(A) tail, a process known as deadenylation, is thought to be the first and rate-limiting step of mRNA turnover. Deadenylation is performed by the Pan2-Pan3 and Ccr4-Not complexes that contain highly conserved exonuclease enzymes Pan2, and Ccr4 and Caf1, respectively. These complexes have been extensively studied, but the mechanisms of how the deadenylase enzymes recognize the poly(A) tail were poorly understood until recently. Here, we summarize recent work from our laboratory demonstrating that the highly conserved Pan2 exonuclease recognizes the poly(A) tail, not through adenine-specific functional groups, but through the conformation of poly(A) RNA. Our biochemical, biophysical, and structural investigations suggest that poly(A) forms an intrinsic base-stacked, single-stranded helical conformation that is recognized by Pan2, and that disruption of this structure inhibits both Pan2 and Caf1. This intrinsic structure has been shown to be important in poly(A) recognition in other biological processes, further underlining the importance of the unique conformation of poly(A).
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A poly(A) tail of optimal length can improve translation efficiency and mRNA stability.
“A poly(A) tail of optimal length can improve translation efficiency and mRNA stability.150,151”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [150]
In mammalian cells, actively translated mRNAs generally contain 100-250 adenosine residues.
“In mammalian cells, actively translated mRNAs generally contain 100–250 adenosine residues.117,150”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [150]
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Advances in COVID-19 mRNA vaccine development
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- Authors
- Tang, T. T. L., & Passmore, L. A.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Venue
- Cold Spring Harbor Symposia on Quantitative Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2019
- Volume
- 84
- Pages
- 21-30
- ISSN
- 0091-7451 (ISSN-L)
- 1943-4456
- PMC
- PMC7116106
- OpenAlex
- W3016536368
- Cited by
- 29
- References
- 73
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 5
- Type
- posted content
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Cold Spring Harbor Symposia on Quantitative Biology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by)
- Funders
- University of Cambridge
- European Commission (HORIZON2020)
- Medical Research Council (725685, MC_U105192715)
- H2020 European Research Council (725685)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- poly(A) tail, RNA secondary structure, deadenylation, CCR4-NOT complex, mRNA turnover, post-transcriptional regulation
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