RBFOX and PTBP1 proteins regulate the alternative splicing of micro-exons in human brain transcripts

Li, Yang I., Sanchez-Pulido, Luis, Haerty, Wilfried ORCID: https://orcid.org/0000-0003-0111-191X and Ponting, Chris P. (2015) RBFOX and PTBP1 proteins regulate the alternative splicing of micro-exons in human brain transcripts. Genome Research, 25 (1). pp. 1-13. ISSN 1088-9051

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Ninety-four percent of mammalian protein-coding exons exceed 51 nucleotides (nt) in length. The paucity of micro-exons (≤ 51 nt) suggests that their recognition and correct processing by the splicing machinery present greater challenges than for longer exons. Yet, because thousands of human genes harbor processed micro-exons, specialized mechanisms may be in place to promote their splicing. Here, we survey deep genomic data sets to define 13,085 micro-exons and to study their splicing mechanisms and molecular functions. More than 60% of annotated human micro-exons exhibit a high level of sequence conservation, an indicator of functionality. While most human micro-exons require splicing-enhancing genomic features to be processed, the splicing of hundreds of micro-exons is enhanced by the adjacent binding of splice factors in the introns of pre-messenger RNAs. Notably, splicing of a significant number of micro-exons was found to be facilitated by the binding of RBFOX proteins, which promote their inclusion in the brain, muscle, and heart. Our analyses suggest that accurate regulation of micro-exon inclusion by RBFOX proteins and PTBP1 plays an important role in the maintenance of tissue-specific protein–protein interactions.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
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Depositing User: LivePure Connector
Date Deposited: 07 Nov 2020 01:10
Last Modified: 21 Apr 2023 00:50
URI: https://ueaeprints.uea.ac.uk/id/eprint/77585
DOI: 10.1101/gr.181990.114

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