ArticleThe Journal of biological chemistry2008
Growth hormone deficiency and splicing fidelity: two serine/arginine-rich proteins, ASF/SF2 and SC35, act antagonistically.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- Potential antitumoral effects of SRPK1 inhibition through modulation of VEGF splicing in pituitary somatotroph tumoral cells.Frontiers in endocrinology · 2025Article
- Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Review
- Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing.Molecular cell · 2013Article
- Testing for natural selection in human exonic splicing regulators associated with evolutionary rate shifts.Journal of molecular evolution · 2013Article
- The exon 29 c.3535A>T in the alpha-2-macroglobulin gene causing aberrant splice variants is associated with mastitis in dairy cattle.Immunogenetics · 2012Article
- The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.Nucleic acids research · 2012Article
- Atypical retinal degeneration 3 in mice is caused by defective PDE6B pre-mRNA splicing.Vision research · 2012Article
- A syn-anti conformational difference allows SRSF2 to recognize guanines and cytosines equally well.The EMBO journal · 2012Article
- Alternative Splicing of a Novel Inducible Exon Diversifies the CASK Guanylate Kinase Domain.Journal of nucleic acids · 2012Article
- Regulation of alternative splicing within the supraspliceosome.Journal of structural biology · 2012Article
- SR proteins induce alternative exon skipping through their activities on the flanking constitutive exons.Molecular and cellular biology · 2011Article
- Antagonistic roles of four SR proteins in the biosynthesis of alternatively spliced tissue factor transcripts in monocytic cells.Journal of leukocyte biology · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The majority of mutations that cause isolated growth hormone deficiency type II are the result of aberrant splicing of transcripts encoding human growth hormone. Such mutations increase skipping of exon 3 and encode a 17.5-kDa protein that acts as a dominant negative to block secretion of full-length protein produced from unaffected alleles. Previously, we identified a splicing regulatory element in exon 3 (exonic splicing enhancer 2 (ESE2)), but we had not determined the molecular mechanism by which this element prevents exon skipping. Here, we show that two members of the serine/arginine-rich (SR) protein superfamily (ASF/SF2 and SC35) act antagonistically to regulate exon 3 splicing. ASF/SF2 activates exon 3 inclusion, but SC35, acting through a region just downstream of ESE2, can block such activation. These findings explain the disease-causing mechanism of a patient mutation in ESE2 that creates a functional SC35-binding site that then acts synergistically with the downstream SC35 site to produce pathological levels of exon 3 skipping. Although the precedent for SR proteins acting as repressors is established, this is the first example of a patient mutation that creates a site through which an SR protein represses splicing.
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