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