TAIL-seq: Genome-wide Determination of Poly(A) Tail Length and 3′ End Modifications
Open accessAbstract
Global investigation of the 3' extremity of mRNA (3'-terminome), despite its importance in gene regulation, has not been feasible due to technical challenges associated with homopolymeric sequences and relative paucity of mRNA. We here develop a method, TAIL-seq, to sequence the very end of mRNA molecules. TAIL-seq allows us to measure poly(A) tail length at the genomic scale. Median poly(A) length is 50-100 nt in HeLa and NIH 3T3 cells. Poly(A) length correlates with mRNA half-life, but not with translational efficiency. Surprisingly, we discover widespread uridylation and guanylation at the downstream of poly(A) tail. The U tails are generally attached to short poly(A) tails (<25 nt), while the G tails are found mainly on longer poly(A) tails (>40 nt), implicating their generic roles in mRNA stability control. TAIL-seq is a potent tool to dissect dynamic control of mRNA turnover and translational control, and to discover unforeseen features of RNA cleavage and tailing.
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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 [21]
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Cites
RNA-Seq: a revolutionary tool for transcriptomics
Wang, Z., Gerstein, M., & Snyder, M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2484 · Cited by 13,174 · see citing works
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 4× · see citing works
“…lengths do not show any meaningful correlation with protein synthesis rates (measured by metabolic labeling and mass spectrometry and divided by mRNA abundance) (Aviner et al., 2013; Schwanha¨usser et al., 2011)( Figure S4B; p = 0.893 for NIH 3T3, p = 0.449 for HeLa, Pearson’s correlation test).”
InfluentialGene silencing by microRNAs: contributions of translational repression and mRNA decay
Huntzinger, E., & Izaurralde, E. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2936 · Cited by 2,339 · see citing works
Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish
Bazzini, A. A., Lee, M. T., & Giraldez, A. J. (2012) · Science · doi:10.1126/science.1215704 · Cited by 709 · cited 4× · see citing works
“To validate TAIL-seq data further, we carried out high-resolution poly(A) tail assay (Hire-PAT [Bazzini et al., 2012]) on five spike-ins and ten individual mRNAs.”
InfluentialA Network of Multiple Regulatory Layers Shapes Gene Expression in Fission Yeast
Lackner, D. H., Beilharz, T. H., Marguerat, S., Mata, J., Watt, S., Schubert, F., Preiss, T., & Bähler, J. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.002 · Cited by 204 · see citing works
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Research works printed but not linked: 2
- Henriksson, N., Nilsson, P., Wu, M., Song, H., and Virtanen, A. (2010). Recognition of adenosine residues by the active site of poly(A)-specific ribonu- clease. J. Biol. Chem. 285, 163-170. Molecular Cell Sequencing the 3 0 Extremity of Messenger RNAs Molecular Cell 53, 1044-1052, March 20, 2014 ª2014 Elsevier Inc. 1051
- Wu, L., Fan, J., and Belasco, J.G. (2006). MicroRNAs direct rapid deadeny- lation of mRNA. Proc. Natl Acad. Sci. USA 103, 4034-4039.
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Jonas, S., & Izaurralde, E. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3965 · Cited by 1,872 · see citing works
Tools for translation: non-viral materials for therapeutic mRNA delivery
Hajj, K. A., & Whitehead, K. A. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2017.56 · Cited by 799 · see citing works
The challenge and prospect of mRNA therapeutics landscape
Weng, Y., Li, C., Yang, T., Hu, B., Zhang, M., Guo, S., Xiao, H., Liang, X.-J., & Huang, Y. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107534 · Cited by 417 · see citing works
Translation affects mRNA stability in a codon-dependent manner in human cells
Wu, Q., Medina, S. G., Kushawah, G., DeVore, M. L., Castellano, L. A., Hand, J. M., Wright, M., & Bazzini, A. A. (2019) · eLife · doi:10.7554/elife.45396 · Cited by 283 · see citing works
A tale of non-canonical tails: gene regulation by post-transcriptional RNA tailing
Yu, S., & Kim, V. N. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0246-8 · Cited by 142 · see citing works
Self-citationStructural and molecular mechanisms for the control of eukaryotic 5′–3′ mRNA decay
Mugridge, J. S., Coller, J., & Gross, J. D. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0164-z · Cited by 133 · see citing works
RNA-binding proteins in neurodegeneration: Seq and you shall receive
Nussbacher, J. K., Batra, R., Lagier-Tourenne, C., & Yeo, G. W. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.02.003 · Cited by 115 · see citing works
Youn, H., & Chung, J.-K. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2015.1057563 · Cited by 114 · see citing works
Non-immunotherapy application of LNP-mRNA: Maximizing efficacy and safety
Vlatkovic, I. (2021) · Biomedicines · doi:10.3390/biomedicines9050530 · Cited by 112 · see citing works
Recognition of Poly(A) RNA through Its Intrinsic Helical Structure
Tang, T. T. L., & Passmore, L. A. (2019) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2019.84.039818 · Cited by 29 · see citing works
Medjmedj, A., Genon, H., Hezili, D., Loth, A. N., Clemençon, R., Guimpied, C., Mollet, L., Bigot, A., Wien, F., Hamacek, J., et al. (2025) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2025.102648 · Cited by 19 · see citing works
- Authors
- Chang, H., Lim, J., Ha, M., & Kim, V. N.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Kim, V. Narry
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 53
- Issue
- 6
- Pages
- 1044-1052
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2072770570
- Cited by
- 454
- References
- 5
- Citations by year
- 2026: 23 · 2025: 32 · 2024: 33 · 2023: 46 · 2022: 48 · 2021: 50 · 2020: 34 · 2019: 41 · 2018: 42 · 2017: 26 · 2016: 31 · 2015: 29 · 2014: 17 · 2013: 1
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Ministry of Education
- Ministry of Science, ICT and Future Planning
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- TAIL-seq, poly(A) tail length, mRNA 3' end, uridylation, guanylation, mRNA stability, mRNA half-life, translation efficiency, mRNA turnover, RNA cleavage
- MeSH terms
- Animals, Base Sequence, Gene Expression Regulation, Guanine, Half-Life, HeLa Cells, Humans, Molecular Sequence Data, Uridine, Signal Transduction, Genome, Sequence Analysis, RNA, 3' Untranslated Regions, RNA Stability, Polyadenylation, MicroRNAs, NIH 3T3 Cells, Mice
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