The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover
Open accessAbstract
Understanding the biologic role of N6-methyladenosine (m 6 A) RNA modifications in mRNA requires an understanding of when and where in the life of a pre-mRNA transcript the modifications are made. We found that HeLa cell chromatin-associated nascent pre-mRNA (CA-RNA) contains many unspliced introns and m 6 A in exons but very rarely in introns. The m 6 A methylation is essentially completed upon the release of mRNA into the nucleoplasm. Furthermore, the content and location of each m 6 A modification in steady-state cytoplasmic mRNA are largely indistinguishable from those in the newly synthesized CA-RNA or nucleoplasmic mRNA. This result suggests that quantitatively little methylation or demethylation occurs in cytoplasmic mRNA. In addition, only ∼10% of m 6 As in CA-RNA are within 50 nucleotides of 5′ or 3′ splice sites, and the vast majority of exons harboring m 6 A in wild-type mouse stem cells is spliced the same in cells lacking the major m 6 A methyltransferase Mettl3. Both HeLa and mouse embryonic stem cell mRNAs harboring m 6 As have shorter half-lives, and thousands of these mRNAs have increased half-lives (twofold or more) in Mettl3 knockout cells compared with wild type. In summary, m 6 A is added to exons before or soon after exon definition in nascent pre-mRNA, and while m 6 A is not required for most splicing, its addition in the nascent transcript is a determinant of cytoplasmic mRNA stability.
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Citations
Cites
N6-methyladenosine-dependent regulation of messenger RNA stability
Wang, X., Lu, Z., Gomez, A., Hon, G. C., Yue, Y., Han, D., Fu, Y., Parisien, M., Dai, Q., Jia, G., et al. (2014) · Nature · doi:10.1038/nature12730 · Cited by 4,558 · cited 4×
“The YTHDF2 RNA-binding protein was then used to collect m 6 A-containing mRNAs for study (Wang et al. 2014a).”
InfluentialComprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons
Meyer, K. D., Saletore, Y., Zumbo, P., Elemento, O., Mason, C. E., & Jaffrey, S. R. (2012) · Cell · doi:10.1016/j.cell.2012.05.003 · Cited by 4,223
ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility
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Self-citationN6-methyladenosine Modulates Messenger RNA Translation Efficiency
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A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation
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Nuclear m6A Reader YTHDC1 Regulates mRNA Splicing
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HITS-CLIP yields genome-wide insights into brain alternative RNA processing
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“…by m 6 A-specific antibody, cross-linking by UV irradiation of the bound RNA to antibody, collection of the bound complex, and release of methylated RNA by protein digestion followed by cDNA library construction and RNA sequencing (RNA-seq) (Ule et al. 2003; Licatalosi et al. 2008).”
Self-citationiCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution
König, J., Zarnack, K., Rot, G., Curk, T., Kayikci, M., Zupan, B., Turner, D. J., Luscombe, N. M., & Ule, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1838 · Cited by 1,126
CLIP Identifies Nova-Regulated RNA Networks in the Brain
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“Extensive T 1/2 measurements for individual sequenced mammalian mRNAs that are available after actinomycin D treatment of cultured cells suggest a wide spectrum of T 1/2 s, from as little as ≤ 1 h to ≥ 10 h (Yang et al. 2003; Sharova et al. 2009; Tani et al. 2012).”
Cited by
Reading, writing and erasing mRNA methylation
Zaccara, S., Ries, R. J., & Jaffrey, S. R. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0168-5 · Cited by 2,597
YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs
Roundtree, I. A., Luo, G.-Z., Zhang, Z., Wang, X., Zhou, T., Cui, Y., Sha, J., Huang, X., Guerrero, L., Xie, P., et al. (2017) · eLife · doi:10.7554/elife.31311 · Cited by 1,256
m 6 A RNA methylation: from mechanisms to therapeutic potential
He, P. C., & He, C. (2021) · The EMBO Journal · doi:10.15252/embj.2020105977 · Cited by 786
Thiol-linked alkylation for the metabolic sequencing of RNA
Herzog, V. A., Reichholf, B., Neumann, T., Rescheneder, P., Bhat, P., Burkard, T. R., Wlotzka, W., von Haeseler, A., Zuber, J., & Ameres, S. L. (2017) · doi:10.1101/177642 · Cited by 622
Thiol-linked alkylation of RNA to assess expression dynamics
Herzog, V. A., Reichholf, B., Neumann, T., Rescheneder, P., Bhat, P., Burkard, T. R., Wlotzka, W., von Haeseler, A., Zuber, J., & Ameres, S. L. (2017) · Nature Methods · doi:10.1038/nmeth.4435 · Cited by 622
Metadata
- Authors
- Ke, S., Pandya-Jones, A., Saito, Y., Fak, J. J., Vågbø, C. B., Geula, S., Hanna, J. H., Black, D. L., Darnell, J. E., & Darnell, R. B.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2017-05-15
- Volume
- 31
- Issue
- 10
- Pages
- 990-1006
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2632544498
- Cited by
- 542
- References
- 11
- Type
- posted content
- Language
- en
- Open access
- diamond
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- The paper
- Ke, S., Pandya-Jones, A., Saito, Y., Fak, J. J., Vågbø, C. B., Geula, S., Hanna, J. H., Black, D. L., Darnell, J. E., & Darnell, R. B. (2017). m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes & Development. https://doi.org/10.1101/gad.301036.117
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