An unappreciated role for RNA surveillance
Open accessAbstract
BACKGROUND: Nonsense-mediated mRNA decay (NMD) is a eukaryotic mRNA surveillance mechanism that detects and degrades mRNAs with premature termination codons (PTC+ mRNAs). In mammals, a termination codon is recognized as premature if it lies more than about 50 nucleotides upstream of the final intron position. More than a third of reliably inferred alternative splicing events in humans have been shown to result in PTC+ mRNA isoforms. As the mechanistic details of NMD have only recently been elucidated, we hypothesized that many PTC+ isoforms may have been cloned, characterized and deposited in the public databases, even though they would be targeted for degradation in vivo. RESULTS: We analyzed the human alternative protein isoforms described in the SWISS-PROT database and found that 144 (5.8% of 2,483) isoform sequences amenable to analysis, from 107 (7.9% of 1,363) SWISS-PROT entries, derive from PTC+ mRNA. CONCLUSIONS: For several of the PTC+ isoforms we identified, existing experimental evidence can be reinterpreted and is consistent with the action of NMD to degrade the transcripts. Several genes with mRNA isoforms that we identified as PTC+--calpain-10, the CDC-like kinases (CLKs) and LARD--show how previous experimental results may be understood in light of NMD.
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IR has been overlooked as a means of normal gene regulation.
“As a result, IR has been overlooked as a means of normal gene regulation (Bicknell et al., 2012; Hillman et al., 2004”
From Orchestrated Intron Retention Regulates Normal Granulocyte Differentiation (2013) · cites this paper as Hillman et al., 2004
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- Authors
- Hillman, R. T., Green, R. E., & Brenner, S. E.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Brenner, Steven E
- Venue
- Genome Biology
- Published
- 2004-02-02
- Volume
- 5
- Issue
- 2
- Pages
- R8-R8
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC395752
- OpenAlex
- W2132865063
- Cited by
- 193
- References
- 66
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 8 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 10 · 2012: 12
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genome biology (publishedVersion)
- PubMed Central (publishedVersion, other-oa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (K22-HG00056, T32HG00047, K22HG000056, T32HG000047)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- nonsense-mediated mRNA decay, mRNA surveillance, premature stop codon, alternative splicing, Swiss-Prot, CAPN10, lard
- MeSH terms
- Calpain, Humans, RNA, Messenger, Alternative Splicing, Codon, Nonsense, Cyclin-Dependent Kinases, Protein Isoforms, RNA Stability, Databases, Protein
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