KHDRBS3
Description
The KHDRBS3 (KH RNA binding domain containing, signal transduction associated 3) is a protein-coding gene located on chromosome 8.
KH domain-containing, RNA-binding, signal transduction-associated protein 3 is a protein that in humans is encoded by the KHDRBS3 gene. KHDRBS3 has been shown to interact with SIAH1. KHDRBS3 interacts with splicing protein Sam68 and oncogene metadherin in prostate cancer cells. KHDRBS3 (T-STAR) expression has been shown to be increased in prostate cancer tissue compared to the surrounding benign tissue. Expression of KHDRBS3 correlates with mpMRI signal measured through Likert score a system similar to PI-RADS. While still under debate, mpMRI signal correlates with higher Gleason grade and tumour size, in addition to histopathological features associated with clinically aggressive prostate cancer. Expression of KHDRBS3 was increased in the failing human myocardium of heart failure patients, here KHDRBS3 protein interacted with several important mRNAs coding for sarcomere components, such as actin gamma 1 (ACTG1), myosin light chain 2 (MYL2), ryanodine receptor 2 (RYR2), troponin I3 (TNNI3), troponin T2 (TNNT2), tropomyosin 1 (TPM1), tropomyosin 2 (TPM2), and titin (TTN). In prostate cancer cell lines KHDRBS3 appears to be androgen regulated, with a reduction in mRNA expression occurring following addition of synthetic androgen R1881 to cells. KHDRBS3 regulates the alternative mRNA splicing of the sacromere protein titin (TTN), leading to intron retention. Overexpression of KHDRBS3 in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) increased Ca2+ transient amplitude and resulted in an increase of Fmax.
KHDRBS3 is an RNA-binding protein that regulates alternative splicing by influencing mRNA splice site selection and exon inclusion. It preferentially binds to the 5'-[AU]UAAA-3' motif in vitro and binds optimally to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. It also binds poly(A). Its RNA-binding abilities are down-regulated by tyrosine kinase PTK6. KHDRBS3 is involved in splice site selection of vascular endothelial growth factor and regulates CD44 alternative splicing by direct binding to purine-rich exonic enhancer. It can regulate alternative splicing of neurexins NRXN1-3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners such as neuroligins and LRRTM family members. Targeted, cell-type specific splicing regulation of NRXN1 at AS4 is involved in neuronal glutamatergic synapse function and plasticity. KHDRBS3 may regulate expression of KHDRBS2/SLIM-1 in defined brain neuron populations by modifying its alternative splicing and can bind FABP9 mRNA. It may play a role as a negative regulator of cell growth and inhibits cell proliferation.
KHDRBS3 is also known as Etle, SALP, SLM-2, SLM2, T-STAR, TSTAR, etoile.
