RNA-binding proteins RBM20 and PTBP1 regulate the alternative splicing of FHOD3. (January 2019)

• Record Type: Journal Article
• Authors: Lorenzi, P.; Sangalli, A.; Fochi, S.; Dal Molin, A.; Malerba, G.; Zipeto, D.; Romanelli, M.G.
• Is Part Of: International journal of biochemistry & cell biology. Volume 106(2019)
• Page Start: 74
• Page End: 83
• Publication Date: 2019-01
• Subjects: aa amino acid -- cDNA complementary DNA -- CUGBP1 CUG-binding protein 1 -- DCM dilated cardiomyopathy -- DID diaphanous inhibitory domain -- DMEM Dulbecco's modified Eagles medium -- FHOD3 formin homology 2 domain containing protein 3 -- GAPDH GlycerAldeides-3-phosphate DeHydrogenase -- GBD GTPase-binding domain -- GFP green fluorescent protein -- hnRNP heterogeneous nuclear ribonucleoprotein -- MBNL1 muscleblind-like protein 1 -- nPTB neuronal polypyrimidine-tract binding protein -- PCR polymerase chain reaction -- PTBP1 polypyrimidine-tract binding protein 1 -- RBM20 RNA binding motif protein 20 -- RIP RNA ImmunoPrecipitation -- RNP RiboNucleoProtein -- RRM RNA Recognition Motif -- RS Arginine Serine domain -- RT-PCR reverse transcription polymerase chain reaction -- RBFOX1 RNA binding protein fox-1 homolog 1 -- snRNPs small nuclear ribonucleoproteins -- TTN Titin; RBM20 -- FHOD3 -- Alternative splicing -- PTBP1 -- RRM -- Sarcomere; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2018.11.009
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Regulation of alternative splicing events is an essential step required for the expression of functional cytoskeleton and sarcomere proteins in cardiomyocytes. About 3% of idiopathic dilated cardiomyopathy cases present mutations in the RNA binding protein RBM20, a tissue specific regulator of alternative splicing. Transcripts expressed preferentially in skeletal and cardiac muscle, including TTN, CAMK2D, LDB3, LMO7, PDLIM3, RTN4, and RYR2, are RBM20-dependent splice variants. In the present study, we investigated the RBM20 involvement in post-transcriptional regulation of splicing variants expressed by Formin homology 2 domain containing 3 ( FHOD3) gene. FHOD3 is a sarcomeric protein highly expressed in the cardiac tissue and required for the assembly of the contractile apparatus. Recently, FHOD3 mutations have been found associated with heart diseases. We identified novel FHOD 3 splicing variants differentially expressed in human tissues and provided evidences that FHOD3 transcripts are specific RBM20 and PTBP1 targets. Furthermore, we demonstrated that the expression of RBM20 and PTBP1 promoted the alternative shift, from inclusion to exclusion, of selected FHOD3 exons. These results indicate that RBM20 and PTBP1 play a role in the actin filament functional organization mediated by FHOD3 isoforms and suggest their possible involvement in heart diseases.