RBM20
Function
RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH (PubMed:22466703, PubMed:24960161, PubMed:26604136, PubMed:27496873, PubMed:27531932, PubMed:29895960, PubMed:30948719, PubMed:32840935, PubMed:34732726, PubMed:35427468). Acts as a repressor of mRNA splicing: specifically binds the 5'UCUU-3' motif that is predominantly found within intronic sequences of pre-mRNAs, leading to the exclusion of specific exons in target transcripts (PubMed:24960161, PubMed:30948719, PubMed:34732726). RBM20-mediated exon skipping is hormone-dependent and is essential for TTN isoform transition in both cardiac and skeletal muscles (PubMed:27531932, PubMed:30948719). RBM20-mediated exon skipping of TTN provides substrates for the formation of circular RNA (circRNAs) from the TTN transcripts (PubMed:27531932, PubMed:34732726). Together with RBM24, promotes the expression of short isoforms of PDLIM5/ENH in cardiomyocytes (By similarity).
Involvement in disease
Cardiomyopathy, dilated, 1DD
CMD1DD
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
None
The disease is caused by variants affecting the gene represented in this entry.
Left ventricular non-compaction (LVNCX): A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation regulates the subcellular localization (PubMed:35427468). Phosphorylation of Ser-635 and Ser-637 in the RS (arginine/serine-rich) region promotes nuclear localization of the protein (PubMed:35427468). In contrast, phosphorylation of the C-terminal disordered region promotes localization to cytoplasmic ribonucleoprotein granules (PubMed:35427468).
Tissue Specificity
Mainly expressed in the heart (PubMed:19712804, PubMed:23886709). Also expressed in skeletal muscle tissues, ovary, small intestine and colon (PubMed:23886709).
Cellular localization
- Nucleus
- Cytoplasm
- Cytoplasmic ribonucleoprotein granule
- The active form that regulates alternative splicing localizes to the nucleus (PubMed:33188278, PubMed:34732726, PubMed:35427468). Also localizes to cytoplasmic ribonucleoprotein granules; localization to cytoplasmic ribonucleoprotein granules plays an important regulatory role (PubMed:33188278, PubMed:34732726, PubMed:35427468). Subcellular localization is regulated by phosphorylation of different parts of the protein: while phosphorylation of the RS (arginine/serine-rich) region promotes nuclear localization, phosphorylation of the C-terminal disordered region promotes localization to cytoplasmic ribonucleoprotein granules (PubMed:35427468).
Alternative names
RNA-binding protein 20, RNA-binding motif protein 20, RBM20