Get started
Work

Accurate Splicing of HDAC6 Requires Son

Year: 2013
Type: article
Abstract: Accurate Splicing of HDAC6 Requires Son.Pre-mRNA splicing requires proper splice site selection mediated by many factors including snRNPs and serine-arginine rich (SR) splicing factors.Son is the largest known SR splicing factor, and it has several putative functional domains including an RS domain, a glycine rich patch (Gpatch) and double stranded RNA binding domain (DSRBD).One-third of Son's amino acid sequence consists of novel repetitive sequence motifs of unknown function (Sharma et al., 2010).Son is essential for organization of pre-mRNA processing factors in nuclear speckles and for cell cycle progression (Sharma et al., 2010;Sharma et al., 2011;Ahn et al 2011).Exon array analysis of Son-depleted HeLa cells revealed changes in 1061 transcripts showing exon inclusion or exclusion, and a total of 2067 splicing events that are potentially regulated by Son.We validated that Son is required for appropriate splice site choice in transcripts for several chromatinmodifying enzymes, including HDAC6, ADA and SETD8 (Sharma et al., 2011).However, the mechanism by which Son maintains accurate splicing is unknown.We are systematically generating model minigene cassettes for molecular and in situ analysis of Son-dependent splicing regulation.We have constructed a HDAC6 minigene reporter that contains the genomic sequence spanning exons 26 through 29.Following Son depletion in HeLa cells transiently transfected with the HDAC6 minigene reporter construct, we observed skipping of exons 27 and 28 on both the reporter and endogenous HDAC6 transcripts.Stable cell lines constructed using HDAC6 minigene reporter construct showed exclusion of exons 27 and 28 upon Son depletion.In order to study Sondependent splicing on HDAC6 in situ, we aimed to localize splicing factor recruitment to the
Language: English
Open Access status: green
OpenAlex ID: W2545099318
FWCI:
Cites: 44
Cited by:
Related to: 10