Promotion of exon 6 inclusion in HuD pre-mRNA by Hu protein family members
Open accessAbstract
The Hu RNA-binding protein family consists of four members: HuR/A, HuB, HuC and HuD. HuR expression is widespread. The other three neuron-specific Hu proteins play an important role in neuronal differentiation through modulating multiple processes of RNA metabolism. In the splicing events examined previously, Hu proteins promote skipping of the alternative exons. Here, we report the first example where Hu proteins promote inclusion of an alternative exon, exon 6 of the HuD pre-mRNA. Sequence alignment analysis indicates the presence of several conserved AU-rich sequences both upstream and downstream to this alternatively spliced exon. We generated a human HuD exon 6 mini-gene reporter construct that includes these conserved sequences. Hu protein over-expression led to significantly increased exon 6 inclusion from this reporter and endogenous HuD. Studies using truncated and mutant HuD exon 6 reporters demonstrate that two AU-rich sequences located downstream of exon 6 are important. RNAi knockdown of Hu proteins decreased exon 6 inclusion. An in vitro splicing assay indicates that Hu proteins promote HuD exon 6 inclusion directly at the level of splicing. Our studies demonstrate that Hu proteins can function as splicing enhancers and expand the functional role of Hu proteins as splicing regulators.
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All four Hu members promote inclusion of HuD exon 6 by binding to two ARE sequences in the downstream intron.
“For instance, all four Hu members were shown to promote inclusion of HuD exon 6 by binding to two ARE sequences in the downstream intron (Wang et al. 2010).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Wang et al. 2010
One functional consequence of HuD auto-regulatory binding is presumably in controlling alternative splicing of its own pre-mRNA.
“One functional consequence of this auto-regulatory binding is presumably in controlling alternative splicing of its own pre-mRNA (see above) (Wang et al. 2010).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Wang et al. 2010
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- Authors
- Wang, H., Molfenter, J., Zhu, H., & Lou, H.
- Affiliations
- Case Western Reserve University (US)
- Case Comprehensive Cancer Center (US)
- Corresponding author
- Lou, Hua
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-02-16
- Volume
- 38
- Issue
- 11
- Pages
- 3760-3770
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC2887941
- OpenAlex
- W2137368340
- Cited by
- 49
- References
- 48
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 3 · 2021: 3 · 2020: 3 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 9 · 2012: 5
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- U.S. Department of Defense
- American Heart Association
- Case Western Reserve University
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R56NS049103, R01NS049103, NS-049103)
- National Center for Research Resources (S10RR024536)
- 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
- HUD, HU protein, alternative splicing, exon inclusion, exon 6, AU-rich elements, splicing enhancers, RNA-binding proteins, pre-mRNA splicing regulation, HuR, hubs, HuC
- MeSH terms
- ELAV-Like Protein 3, ELAV-Like Protein 4, Adenine, Base Sequence, Cell Line, Exons, Humans, Introns, Molecular Sequence Data, RNA Precursors, RNA, Messenger, Uracil, Sequence Alignment, Conserved Sequence, Alternative Splicing, Regulatory Sequences, Ribonucleic Acid, ELAV Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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