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fus/TLS orchestrates splicing of developmental regulators during gastrulation
Darwin S Dichmann1, Richard M Harland
1Department of Molecular and Cell Biology, Center for Integrative Genomics, University of California at Berkeley, Berkeley, California 94720, USA.
Genes & Development
|June 21, 2012
Summary
The RNA-binding protein fus is crucial for early frog development, ensuring proper mRNA splicing of key developmental genes. Its absence causes developmental defects by leading to intron retention in critical transcripts.
Area of Science:
- Developmental Biology
- Molecular Biology
- RNA Biology
Background:
- The RNA-binding protein fus/TLS (fused in sarcoma/translocated in sarcoma) plays a role in various cellular processes.
- Its specific function during early vertebrate embryogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the role of fus in early frog development, focusing on its impact on mRNA splicing and embryogenesis.
- To identify specific developmental genes regulated by fus and the molecular mechanisms underlying developmental defects.
Main Methods:
- Fus knockdown in frog embryos.
- Analysis of mRNA splicing patterns using RNA sequencing (RNA-seq).
- Gene ontology (GO) slim annotation analysis.
Main Results:
- Fus knockdown leads to failed gastrulation and defective mesodermal differentiation.
- Intron retention in fibroblast growth factor 8 (fgf8), fgf receptor 2 (fgfr2), and cadherin 1 (cdh1) transcripts was observed.
- RNA-seq revealed 3%-5% of all transcripts exhibited intron retention, with affected genes enriched for developmental regulators.
Conclusions:
- Fus is essential for proper mRNA splicing of developmental genes during early frog embryogenesis.
- Fus-mediated regulation of splicing is critical for gastrulation and cell adhesion.
- These findings highlight fus's central role in embryogenesis and offer insights into its potential involvement in neurodegenerative diseases.
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