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To RNA-binding and beyond: Emerging facets of the role of Rbfox proteins in development and disease

Mukherjee, A and Nongthomba, U (2023) To RNA-binding and beyond: Emerging facets of the role of Rbfox proteins in development and disease. In: Wiley Interdisciplinary Reviews: RNA .

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Official URL: https://doi.org/10.1002/wrna.1813


The RNA-binding Fox-1 homologue (Rbfox) proteins represent an ancient family of splicing factors, conserved through evolution. All members share an RNA recognition motif (RRM), and a particular affinity for the GCAUG signature in target RNA molecules. The role of Rbfox, as a splice factor, deciding the tissue-specific inclusion/exclusion of an exon, depending on its binding position on the flanking introns, is well known. Rbfox often acts in concert with other splicing factors, and forms splicing regulatory networks. Apart from this canonical role, recent studies show that Rbfox can also function as a transcription co-factor, and affects mRNA stability and translation. The repertoire of Rbfox targets is vast, including genes involved in the development of tissue lineages, such as neurogenesis, myogenesis, and erythropoeiesis, and molecular processes, including cytoskeletal dynamics, and calcium handling. A second layer of complexity is added by the fact that Rbfox expression itself is regulated by multiple mechanisms, and, in vertebrates, exhibits tissue-specific expression. The optimum dosage of Rbfox is critical, and its misexpression is etiological to various disease conditions. In this review, we discuss the contextual roles played by Rbfox as a tissue-specific regulator for the expression of many important genes with diverse functions, through the lens of the emerging data which highlights its involvement in many human diseases. Furthermore, we explore the mechanistic details provided by studies in model organisms, with emphasis on the work with Drosophila. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Turnover and Surveillance > Regulation of RNA Stability RNA Processing > Splicing Regulation/Alternative Splicing. © 2023 Wiley Periodicals LLC.

Item Type: Journal Article
Publication: Wiley Interdisciplinary Reviews: RNA
Publisher: John Wiley and Sons Inc
Additional Information: The copyright for this article belongs to the John Wiley and Sons Inc.
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 28 Oct 2023 07:51
Last Modified: 28 Oct 2023 07:51
URI: https://eprints.iisc.ac.in/id/eprint/83162

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