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Alternative RNA Splicing02:18

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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
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RNA-binding proteins RBM20 and PTBP1 regulate the alternative splicing of FHOD3.

P Lorenzi1, A Sangalli1, S Fochi1

  • 1Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Italy.

The International Journal of Biochemistry & Cell Biology
|November 24, 2018
PubMed
Summary

RNA binding protein RBM20 regulates alternative splicing in cardiomyocytes. This study shows RBM20 and PTBP1 control FHOD3 splicing variants, impacting actin organization and potentially heart disease.

Keywords:
Alternative splicingFHOD3PTBP1RBM20RRMSarcomere

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Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Gene Regulation

Background:

  • Alternative splicing is crucial for cardiomyocyte function, particularly for cytoskeletal and sarcomeric proteins.
  • Mutations in RNA binding protein RBM20, a key splicing regulator, are linked to idiopathic dilated cardiomyopathy.
  • FHOD3, a sarcomeric protein vital for cardiac contractile apparatus assembly, has recently been associated with heart diseases.

Purpose of the Study:

  • To investigate the role of RBM20 in the post-transcriptional regulation of splicing variants of the Formin homology 2 domain containing 3 (FHOD3) gene.
  • To identify novel FHOD3 splicing variants and determine if they are targets of RBM20 and PTBP1.
  • To elucidate the functional impact of RBM20 and PTBP1 on FHOD3 alternative splicing.

Main Methods:

  • Identification and characterization of FHOD3 splicing variants across different human tissues.
  • Experimental validation of FHOD3 transcripts as targets for RBM20 and PTBP1.
  • Analysis of the effect of RBM20 and PTBP1 expression on FHOD3 exon splicing patterns.

Main Results:

  • Discovery of novel FHOD3 splicing variants with differential tissue expression.
  • Confirmation that FHOD3 transcripts are direct targets of RBM20 and PTBP1.
  • Demonstration that RBM20 and PTBP1 induce an alternative splicing switch in FHOD3, shifting from exon inclusion to exclusion.

Conclusions:

  • RBM20 and PTBP1 are key regulators of FHOD3 alternative splicing, influencing the production of specific FHOD3 isoforms.
  • These regulatory events mediated by RBM20 and PTBP1 are important for functional organization of actin filaments via FHOD3.
  • The findings suggest a potential role for RBM20 and PTBP1 in the pathogenesis of heart diseases through FHOD3 regulation.