The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation
Open accessAbstract
We adapted UV CLIP (cross-linking immunoprecipitation) to accurately locate tens of thousands of m 6 A residues in mammalian mRNA with single-nucleotide resolution. More than 70% of these residues are present in the 3′-most (last) exons, with a very sharp rise (sixfold) within 150–400 nucleotides of the start of the last exon. Two-thirds of last exon m 6 A and >40% of all m 6 A in mRNA are present in 3′ untranslated regions (UTRs); contrary to earlier suggestions, there is no preference for location of m 6 A sites around stop codons. Moreover, m 6 A is significantly higher in noncoding last exons than in next-to-last exons harboring stop codons. We found that m 6 A density peaks early in the 3′ UTR and that, among transcripts with alternative polyA (APA) usage in both the brain and the liver, brain transcripts preferentially use distal polyA sites, as reported, and also show higher proximal m 6 A density in the last exons. Furthermore, when we reduced m6A methylation by knocking down components of the methylase complex and then examined 661 transcripts with proximal m6A peaks in last exons, we identified a set of 111 transcripts with altered (approximately two-thirds increased proximal) APA use. Taken together, these observations suggest a role of m 6 A modification in regulating proximal alternative polyA choice.
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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 3×
“With the commercial availability of m6A-specific antibodies and RNA-seq, thousands of m6A residues in human and yeast polyA+ RNA have been reported (Dominissini et al. 2012; Meyer et al. 2012; Fustin et al. 2013; Schwartz et al. 2013, 2014; Wang et al. 2014).”
BackgroundMethodComprehensive 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
N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y.-G., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.687 · Cited by 4,106 · cited 1×
“Furthermore, mutations in one of the human demethylase genes is associated with a phenotype (overweight) (Jia et al. 2011; Zheng et al. 2013).”
BackgroundChromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009) · Nature · doi:10.1038/nature07672 · Cited by 4,098
ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility
Zheng, G., Dahl, J. A., Niu, Y., Fedorcsak, P., Huang, C.-M., Li, C. J., Vågbø, C. B., Shi, Y., Wang, W.-L., Song, S.-H., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.015 · Cited by 3,550
Self-citationA METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation
Liu, J., Yue, Y., Han, D., Wang, X., Fu, Y., Zhang, L., Jia, G., Yu, M., Lu, Z., Deng, X., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1432 · Cited by 3,433
HITS-CLIP yields genome-wide insights into brain alternative RNA processing
Licatalosi, D. D., Mele, A., Fak, J. J., Ule, J., Kayikci, M., Chi, S. W., Clark, T. A., Schweitzer, A. C., Blume, J. E., Wang, X., et al. (2008) · Nature · doi:10.1038/nature07488 · Cited by 1,352 · cited 2×
“In the present work, modifying the HITS (high-throughput sequencing)-CLIP (cross-linking immunoprecipitation) protocol (Licatalosi et al. 2008; Darnell 2010) and selection of m6A antibody-bound oligonucleotides, we describe a precise and generally applicable method to locate specific m6A residues.”
MethodSelf-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
Edmonds, M., Vaughan, M. H., & Nakazato, H. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.6.1336 · Cited by 510
HITS-CLIP: panoramic views of protein-RNA regulation in living cells
Darnell, R. B. (2010) · WIREs RNA · doi:10.1002/wrna.31 · Cited by 382
Self-citation
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
The role of m6A modification in the biological functions and diseases
Jiang, X., Liu, B., Nie, Z., Duan, L., Xiong, Q., Jin, Z., Yang, C., & Chen, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00450-x · Cited by 2,335
The m(6)A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells
Lin, S., Choe, J., Du, P., Triboulet, R., & Gregory, R. I. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.021 · Cited by 1,531
Alternative polyadenylation of mRNA precursors
Tian, B., & Manley, J. L. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.116 · Cited by 1,179
The U6 snRNA m 6 A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention
Pendleton, K. E., Chen, B., Liu, K., Hunter, O. V., Xie, Y., Tu, B. P., & Conrad, N. K. (2017) · Cell · doi:10.1016/j.cell.2017.05.003 · Cited by 1,085
Metadata
- Authors
- Ke, S., Alemu, E. A., Mertens, C., Gantman, E. C., Fak, J. J., Mele, A., Haripal, B., Zucker-Scharff, I., Moore, M. J., Park, C. Y., Vågbø, C. B., Kusśnierczyk, A., Klungland, A., Darnell, J. E., & Darnell, R. B.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2015-09-24
- Volume
- 29
- Issue
- 19
- Pages
- 2037-2053
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2180404227
- Cited by
- 812
- References
- 14
- Type
- posted content
- Language
- en
- Open access
- diamond
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- The paper
- Ke, S., Alemu, E. A., Mertens, C., Gantman, E. C., Fak, J. J., Mele, A., Haripal, B., Zucker-Scharff, I., Moore, M. J., Park, C. Y., Vågbø, C. B., Kusśnierczyk, A., Klungland, A., Darnell, J. E., & Darnell, R. B. (2015). A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation. Genes & Development. https://doi.org/10.1101/gad.269415.115
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