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Updated: Aug 5, 2026
10:25
Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
Cytoplasmic RBM20 granules modulate non-RBM20 target splicing through interactions with other splicing factors
Yanghai Zhang1, Zachery R Gregorich1, Chunling Liu1
1Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706, United States.
Nucleic Acids Research
|August 4, 2026
Summary
Pathogenic variants in RNA-binding motif protein 20 (RBM20) cause cytoplasmic granules, impacting splicing. This study defines granule composition and shows cytoplasmic RBM20 affects splicing of non-target genes.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- RNA-binding motif protein 20 (RBM20) is a crucial splicing factor.
- Pathogenic RBM20 variants lead to aberrant cytoplasmic granule formation.
- The precise composition and function of RBM20 compartments remain largely unknown.
Purpose of the Study:
- To elucidate the proteomic composition of RBM20 nuclear speckles and cytoplasmic granules.
- To investigate the functional consequences of RBM20 compartmentalization on splicing regulation.
- To determine the role of cytoplasmic RBM20 granules in disease pathogenesis.
Main Methods:
- In situ proximity labeling proteomics to identify RBM20-associated proteins.
- Co-localization and immunoprecipitation assays to validate protein interactions.
- Analysis of splicing defects in mouse models with pathogenic RBM20 variants.
Main Results:
- Identified distinct protein sets for RBM20 nuclear speckles (splicing/transcription factors) and cytoplasmic granules (cytoplasmic proteins).
- Confirmed co-localization of CELF1 and MBNL2 in both RBM20 compartments.
- Observed disrupted CELF1/MBNL2 splicing in pathogenic RBM20 variant mice, correlating with cytoplasmic granules.
Conclusions:
- RBM20 nuclear speckles and cytoplasmic granules possess unique proteomic profiles.
- Cytoplasmic RBM20 granules contribute to splicing dysregulation, affecting non-RBM20 targets.
- Targeting cytoplasmic RBM20 granule formation may offer therapeutic potential for RBM20-related disorders.
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