Rbfox Proteins Regulate Splicing as Part of a Large Multiprotein Complex LASR

Area of Science:

• Molecular Biology
• Neuroscience
• Genetics

Background:

• Rbfox proteins are key regulators of alternative splicing and posttranscriptional regulation in the mammalian brain.
• Their diverse roles suggest complex protein-protein interactions, crucial for understanding neurological disease mechanisms.

Purpose of the Study:

• To investigate the protein interactions of Rbfox proteins in the mammalian brain.
• To identify the composition and function of complexes involving Rbfox proteins.

Main Methods:

• Identification of Rbfox-associated proteins using co-immunoprecipitation and mass spectrometry.
• In vivo crosslinking to map Rbfox binding sites.
• Analysis of splicing repression assays.

Main Results:

• Rbfox proteins form a large assembly of splicing regulators (LASR) with hnRNP M, hnRNP H, hnRNP C, Matrin3, NF110/NFAR-2, NF45, and DDX5.
• Splicing repression by hnRNP M is enhanced by Rbfox.
• Rbfox and hnRNP M motifs are found in close proximity in vivo, indicating functional association within the LASR complex.

Conclusions:

• Rbfox proteins function within a defined complex of splicing cofactors (LASR).
• This complex regulates a wider range of exons than previously known.
• Understanding the LASR complex is vital for deciphering splicing regulatory codes and their role in neurological disorders.