The Genomic Distribution of Musashi Binding Elements
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The regulation of gene expression is fundamental to developmental and physiological processes. Such regulation occurs at all steps of the central dogma, and post-transcriptional regulation is thought to be a prominent point in the process. Musashi is an RNA-binding protein that is known to post-transcriptionally regulate genes involved in development and cell fate through interaction with the Musashi-binding element (MBE) in target mRNA 3’ UTRs. Given the important ways that Musashi regulates cell fate in humans, this study aims to characterize MBE frequency and distribution and to highlight candidate Musashi targets. The neutral model predicts that, due to their small size (5-7 bp), MBEs commonly occur in the genome resulting in several potential regulatory targets. Moreover, past studies have shown that Musashi’s effect on translation is proportional to the number of MBEs in a target mRNA 3’ UTR. It was found that genome-wide MBEs occur more often than expected by chance in the 3’ UTRs of protein-coding genes. The distribution of MBEs along the length of 3’ UTRs of protein-coding genes was determined to be non-random, with MBEs more likely to appear near the 3’ end of the 3’ UTR, potentially relating to functional interactions between Musashi and poly(A)-binding protein. Finally, genes with counts of MBEs on the 3’ UTR that were greater than random expectation had Gene Ontology terms associated with mRNA processing and post-transcriptional regulation of gene expression. This characterized pattern of MBEs in 3’ UTR of protein-coding genes is thought to reflect selection for Musashi regulation and suggests a large number of previously unappreciated regulatory targets.