A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer.

Abstract

We have purified and cloned a new splicing factor, KSRP. KSRP is a component of a multiprotein complex that binds specifically to an intronic splicing enhancer element downstream of the neuron-specific c-src N1 exon. This 75-kD protein induces the assembly of five other proteins, including the heterogeneous nuclear ribonucleoprotein F, onto the splicing enhancer. The sequence of the KSRP cDNA indicates that the protein contains four K homology RNA-binding domains and an unusual carboxy-terminal domain. KSRP is similar to two proteins, FUSE-binding protein and P-element somatic inhibitor. KSRP is expressed in both neural and non-neural cell lines, although it is present at higher levels in neural cells. Antibodies specific for KSRP inhibit the splicing of the N1 exon in vitro. Moreover, this inhibition of N1 splicing can be rescued by the addition of purified KSRP. KSRP is likely to regulate splicing from a number of intronic splicing enhancer sequences.[Key Words: Alternative splicing; regulatory protein; KSRP; intronic splicing enhancer; RNA-binding protein]

Cloning and characterization of two neural‐salient serine/arginine‐rich (NSSR) proteins involved in the regulation of alternative splicing in neurones

“…A neurone-speci®c splicing factor, KSRP, was isolated and cloned as a protein binding to the intronic enhancer downstream of the N1 c-src exon (Min et al 1997). KSRP is an RNA-binding protein, but does not have an SR domain and is expressed in both neural and non-neural cell lines.…”

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

“…Indeed, we previously identified an AREbinding activity of KSRP (K homology-type splicing regulatory protein), a protein originally identified as a component of a complex assembled on an intronic enhancer required for neuronal-specific c-src splicing (Min et al, 1997). KSRP, an ubiquitously expressed shuttle protein (R. Gherzi and C.Y.…”

KSRP/FUBP2 Is a Binding Protein of GO-Y086, a Cytotoxic Curcumin Analogue

“…KSRP/FUBP2 is implicated in a variety of cellular processes, including splicing in the nucleus, mRNA decay, maturation of miRNA, and transcriptional control of proto-oncogenes such as c-myc. [13][14][15][16] The domain structure of KSRP/FUBP2 consists of a PG-rich amino-terminus, four KH-type nucleic acid-binding domains, and a Q-rich carboxy (C)-terminus ( Figure 4A). 17 To identify the GO-Y086-binding site on KSRP/FUBP2, pull down assays were carried out using different GFP-tagged deletion mutants of KSRP/FUBP2 ( Figure 4B).…”