Disease relevance of SFRS7

• We show that a recombinant 9G8 protein, expressed using a baculovirus vector and excluding other SR factors, rescues the splicing activity of a 9G8-depleted nuclear extract and an S100 cytoplasmic fraction [1].
• These results indicate that 9G8 plays a key role in regulation of exon 10 splicing and imply a pathogenic role in neurodegenerative diseases [2].

Psychiatry related information on SFRS7

• SR protein 9G8 modulates splicing of tau exon 10 via its proximal downstream intron, a clustering region for frontotemporal dementia mutations [2].

High impact information on SFRS7

• Antibodies to SRp20 or 9G8 eliminate RNA binding and significantly inhibit the export of RNAs carrying the element from oocyte nuclei [3].
• Our observation that SRp20 and 9G8 can be UV cross-linked to polyadenylated RNA in both the nucleus and cytoplasm of HeLa cells suggests a more general role for these SR proteins in mRNA export [3].
• Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer [4].
• We present the solution structures of the free 9G8 and SRp20 RNA recognition motifs (RRMs) and of SRp20 RRM in complex with the RNA sequence 5'CAUC3'. The SRp20-RNA structure reveals that although all 4 nt are contacted by the RRM, only the 5' cytosine is primarily recognized in a specific way [5].
• This might explain the numerous consensus sequences found by SELEX (systematic evolution of ligands by exponential enrichment) for the RRM of 9G8 and SRp20 [5].

Biological context of SFRS7

• The identification of the 9G8 factor enlarges the essential family of SR splicing factors, whose members have also been proposed to play key roles in alternative splicing [1].
• Compared with the other SR splicing factors, 9G8 presents some specific sequence features because it contains an RRSRSXSX consensus sequence repeated six times in the SR domain, and a CCHC motif in its median region, similar to the zinc knuckle found in the SLU7 splicing factor in yeast [1].
• We have located the human 9G8 gene in the p22-21 region of chromosome 2 [6].
• Using a two-hybrid interactive screen, the splicing protein 9G8 was identified as an in vivo partner for CDK11(p110) [7].
• Finally, 9G8 is a phosphoprotein in vivo and is a substrate for CDK11(p110) phosphorylation in vitro [7].

Associations of SFRS7 with chemical compounds

• Characterization and cloning of the human splicing factor 9G8: a novel 35 kDa factor of the serine/arginine protein family [1].
• The isolation and characterization of cDNA clones indicate that 9G8 is a novel member of the serine/arginine (SR) splicing factor family because it includes an N-terminal RNA binding domain (RBD) and a C-terminal SR domain [1].
• SRZ proteins are similar to human 9G8 splicing factor because they contain a zinc knuckle, precipitate with 65% ammonium sulfate, and cross-react with the 9G8 monoclonal antibody [8].
• Here we show that a 35-kDa member of the SR protein family, 9G8, can activate the splicing of alpha-tropomyosin exon 2 [9].

Physical interactions of SFRS7

• In addition, we have found that PIR1 interacted with splicing factors 9G8 and SRp30C, possibly through an RNA intermediate during a yeast two-hybrid screen [10].

Other interactions of SFRS7

• This similarity was confirmed by the fact that purified human SC35 also rescues the 9G8-depleted extract [1].
• Finally, activation by ASF/SF2 and 9G8 was found to be independent of the RS domain [11].
• Alternative splicing of intron 3 of the serine/arginine-rich protein 9G8 gene. Identification of flanking exonic splicing enhancers and involvement of 9G8 as a trans-acting factor [12].

References