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a novel mechanism by which SRRM4 drives neuroendocrine prostate cancer progression via a pluripotency gene network, is reported.
data indicate that SRRM4 regulates alternative RNA splicing of the Bif-1 gene that enables PCa cells resistant to apoptotic stimuli under anti-cancer therapies, and may contribute to AdPC progression into t-NEPC.
SRRM4 regulates alternative splicing programs to drive neuroendocrine prostate cancer progression (an aggressive subtype of castration-resistant prostate cancer) under androgen receptor pathway inhibition.
Neuronal activity-dependent microexons are nSR100 targets and are misregulated in autism.
The splicing of REST by SRRM4 could promote the neuroendocrine phenotype in CRPC.
Neural microexons are regulated by the neuronal-specific splicing factor nSR100/SRRM4, through its binding to adjacent intronic enhancer motifs; neural microexons are frequently misregulated in the brains of individuals with autism spectrum disorder, and this misregulation is associated with reduced levels of nSR100.
findings show that nSR100 plays a role in the alternative splicing of REST in small cell lung cancer (SCLC); study provides new insight into the role of nSR100 in the expression of sREST, possibly in the pathogenesis of SCLC
Results suggest that SRRM4 controls neurite outgrowth through regulation of alternative splicing of protrudin transcripts.
Loss of nSR100 impairs development of the central and peripheral nervous systems in part by disrupting neurite outgrowth, cortical layering in the forebrain, and axon guidance in the corpus callosum
required for the continued survival and differentiation of inner and vestibular hair cells past a set point in their development
Srrm4 function is critical in the hearing and balance organs, but not in all neural tissues. Srrm4 is the first alternative-splicing regulator to be associated with hearing. Analysis of bv mice provides exon-level insights into hair-cell development.
role for nSR100 in the inhibition of REST activity, blocking nSR100 expression in the developing mouse brain impairs neurogenesis
Study identified the neural-specific SR-related protein of 100 kDa (nSR100)& shows that nSR100 regulates an extensive network of brain-specific alternative exons enriched in genes that function in neural cell differentiation.
SRRM4 promotes alternative splicing and inclusion of neural-specific exons in target mRNAs (Calarco et al., 2009
medulloblastoma antigen MU-MB-2.76
, neural-specific SR-related protein of 100 kDa
, neural-specific serine/arginine repetitive splicing factor of 100 kDa
, serine/arginine repetitive matrix protein 4
, KIAA1853 protein-like
, serine/arginine repetitive matrix 2C
, serine/arginine repetitive matrix 4
, Neural-specific serine/arginine repetitive splicing factor of 100 kDa