Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene:

SFRS10

splicing factor, arginine/serine-rich 10...

Homo sapiens

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Jiang, Z., Young, P.J., Stoilov, P., Beil, B., Nayler, O., et al.

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Disease relevance of SFRS10

Our results implicate the human tau gene as a target gene for the alternative splicing regulator Tra2 beta, suggesting that Tra2 beta may play a role in aberrant tau exon 10 alternative splicing and in the pathogenesis of tauopathies [1].

High impact information on SFRS10

Overexpression of RNPS1 in HeLa cells induced exon skipping in a model beta-globin pre-mRNA and a human tra-2 beta pre-mRNA [2].
We propose that the regulation of the tra2-beta pre-mRNA alternative splicing provides a robust and sensitive molecular sensor that measures the ratio between HTRA2-BETA1 and its interacting proteins [3].
The resulting HTRA2-BETA3 protein lacks the first RS domain of HTRA2-BETA1, is expressed in several tissues and has no influence on tra2-beta splice site selection [3].
However, correct splicing can be restored by over-expression of the SR-like splicing factor Htra2-beta 1 [4].
We now demonstrate that a second splicing factor, SRp30c, can stimulate SMN exon 7-inclusion and that this activity required the same AG-rich enhancer as hTra2 beta 1 [5].

Biological context of SFRS10

In the absence of the hTra2 beta 1 binding site, SRp30c failed to complex with SMN exon 7 [5].
Biochemical studies including in vitro splicing and RNA interference experiments in transfected cells support a role for Tra2 beta protein in regulating alternative splicing of human tau gene [1].
Human transformer-2-beta gene (SFRS10): complete nucleotide sequence, chromosomal localization, and generation of a tissue-specific isoform [6].

Anatomical context of SFRS10

SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2 beta 1 [5].
The ratio of these two isoforms changes after stimulation of primary human T-cell and primary rat spleen cell cultures, indicating that alternative splicing is involved in regulation of htra2-beta activity [7].

Associations of SFRS10 with chemical compounds

Pilocarpine-induced neuronal activity changes the alternative splicing pattern of the human transformer-2-beta gene in the brain [8].

Physical interactions of SFRS10

Mutations in tau gene exon 10 associated with FTDP-17 alter the activity of an exonic splicing enhancer to interact with Tra2 beta [1].

Other interactions of SFRS10

Tra2 beta, SF2/ASF and SRp30c modulate the function of an exonic splicing enhancer in exon 10 of tau pre-mRNA [9].

References

Mutations in tau gene exon 10 associated with FTDP-17 alter the activity of an exonic splicing enhancer to interact with Tra2 beta. Jiang, Z., Tang, H., Havlioglu, N., Zhang, X., Stamm, S., Yan, R., Wu, J.Y. J. Biol. Chem. (2003)
Human RNPS1 and its associated factors: a versatile alternative pre-mRNA splicing regulator in vivo. Sakashita, E., Tatsumi, S., Werner, D., Endo, H., Mayeda, A. Mol. Cell. Biol. (2004)
Human tra2-beta1 autoregulates its protein concentration by influencing alternative splicing of its pre-mRNA. Stoilov, P., Daoud, R., Nayler, O., Stamm, S. Hum. Mol. Genet. (2004)
Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Brichta, L., Hofmann, Y., Hahnen, E., Siebzehnrubl, F.A., Raschke, H., Blumcke, I., Eyupoglu, I.Y., Wirth, B. Hum. Mol. Genet. (2003)
SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2 beta 1. Young, P.J., DiDonato, C.J., Hu, D., Kothary, R., Androphy, E.J., Lorson, C.L. Hum. Mol. Genet. (2002)
Human transformer-2-beta gene (SFRS10): complete nucleotide sequence, chromosomal localization, and generation of a tissue-specific isoform. Nayler, O., Cap, C., Stamm, S. Genomics (1998)
Molecular cloning of htra2-beta-1 and htra2-beta-2, two human homologs of tra-2 generated by alternative splicing. Beil, B., Screaton, G., Stamm, S. DNA Cell Biol. (1997)
Activity-dependent regulation of alternative splicing patterns in the rat brain. Daoud, R., Da Penha Berzaghi, M., Siedler, F., Hübener, M., Stamm, S. Eur. J. Neurosci. (1999)
Tra2 beta, SF2/ASF and SRp30c modulate the function of an exonic splicing enhancer in exon 10 of tau pre-mRNA. Kondo, S., Yamamoto, N., Murakami, T., Okumura, M., Mayeda, A., Imaizumi, K. Genes Cells (2004)