The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay
Open accessAbstract
Many alternative splicing events create RNAs with premature stop codons, suggesting that alternative splicing coupled with nonsense-mediated decay (AS-NMD) may regulate gene expression post-transcriptionally. We tested this idea in mice by blocking NMD and measuring changes in isoform representation using splicing-sensitive microarrays. We found a striking class of highly conserved stop codon-containing exons whose inclusion renders the transcript sensitive to NMD. A genomic search for additional examples identified >50 such exons in genes with a variety of functions. These exons are unusually frequent in genes that encode splicing activators and are unexpectedly enriched in the so-called “ultraconserved” elements in the mammalian lineage. Further analysis show that NMD of mRNAs for splicing activators such as SR proteins is triggered by splicing activation events, whereas NMD of the mRNAs for negatively acting hnRNP proteins is triggered by splicing repression, a polarity consistent with widespread homeostatic control of splicing regulator gene expression. We suggest that the extreme genomic conservation surrounding these regulatory splicing events within splicing factor genes demonstrates the evolutionary importance of maintaining tightly tuned homeostasis of RNA-binding protein levels in the vertebrate cell.
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Gene Ontology: tool for the unification of biology
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Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
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Mechanisms of Alternative Pre-Messenger RNA Splicing
Black, D. L. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161720 · Cited by 2,704
The UCSC Genome Browser Database
Karolchik, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg129 · Cited by 1,887
Ultraconserved Elements in the Human Genome
Bejerano, G., Pheasant, M., Makunin, I., Stephen, S., Kent, W. J., Mattick, J. S., & Haussler, D. (2004) · Science · doi:10.1126/science.1098119 · Cited by 1,732
Understanding alternative splicing: towards a cellular code
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Predictive Identification of Exonic Splicing Enhancers in Human Genes
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Cited by
Frequent pathway mutations of splicing machinery in myelodysplasia
Yoshida, K., Sanada, M., Shiraishi, Y., Nowak, D., Nagata, Y., Yamamoto, R., Sato, Y., Sato-Otsubo, A., Kon, A., Nagasaki, M., et al. (2011) · Nature · doi:10.1038/nature10496 · Cited by 2,029
Makeyev, E. V., Zhang, J., Carrasco, M. A., & Maniatis, T. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.015 · Cited by 1,395
Context-dependent control of alternative splicing by RNA-binding proteins
Fu, X.-D., & Ares, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3778 · Cited by 1,044
Self-citationFunctional consequences of developmentally regulated alternative splicing
Kalsotra, A., & Cooper, T. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3052 · Cited by 729
RNA splicing factors as oncoproteins and tumour suppressors
Dvinge, H., Kim, E., Abdel-Wahab, O., & Bradley, R. K. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.51 · Cited by 687
Metadata
- Authors
- Ni, J. Z., Grate, L., Donohue, J. P., Preston, C., Nobida, N., O’Brien, G., Shiue, L., Clark, T. A., Blume, J. E., & Ares, M.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-03-15
- Volume
- 21
- Issue
- 6
- Pages
- 708-718
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2157338021
- Cited by
- 549
- References
- 59
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Ni, J. Z., Grate, L., Donohue, J. P., Preston, C., Nobida, N., O’Brien, G., Shiue, L., Clark, T. A., Blume, J. E., & Ares, M. (2007). Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay. Genes & Development. https://doi.org/10.1101/gad.1525507
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