Exploring the Possible Function of miRNA Gene Promoters in Protein Coding Gene Distal Regulation

Undergraduate #16
Discipline: Biological Sciences
Subcategory: Biomedical Engineering

Mary Swadener - University of Washington

MiRNA primary transcripts, or miRNA genes as they will be referred to, are one of the more abundant classes of regulatory genes in the human genome (Bartel, 2004.) They are essential to cell maintenance, coding for molecules that aid in degrading mRNA. Studying the wider regulatory potential of miRNA genes, we utilized data containing peaks in DNase 1 digest cleavage, thought to represent peaks in accessibility to transcription factor binding. We found that a large majority of peaks in miRNA gene promoters were correlated with those in protein coding genes. We hypothesize that miRNA genes may act as distal enhancers that recruit RNA polymerase to protein coding gene promoters. Exploration of this functionality of miRNA promoters will further characterize the role of miRNA genes in the human genome, how they fit into its regulatory networks, and how this may impact human health.
In this work, we have developed a set of python scripts to 1.) derive miRNA promoters based on the TSSs from (de Rie et al) and DNase I sequencing data from a broad range of cell types/conditions and 2.) identify putative distal interactions by searching for elements whose accessibility is correlated with miRNA promoters across these cells/conditions. Our programs have identified 443 miRNA promoters that are correlated (Pearson r >= .7) with the promoter(s) of nearby (< 500,000 kb) protein coding genes, suggesting that these miRNA promoters may act as distal enhancer elements for these genes. Putative miRNA-protein coding promoter interactions will be tested in vivo via genome editing, either by deletion of miRNA promoter elements, or using a synthetic enhancer-promoter reporter system inserted into the AAVS1 safe-harbor locus. References: De Rie et al. (2017). An integrated expression atlas of miRNAs and their promoters in human and mouse. Nat Biotech. advance online publication. Bartel. (2004). MicroRNAs. Cell , Volume 116 , Issue 2 , 281 - 297. Daniel Chee, University of Washington, Seattle, WA, Genome Sciences Department

Not Submitted

Funder Acknowledgement(s): Funding received from Altius Institute for Biomedical Sciences, and the Stamatoyannopoulos Lab, from the University of Washington Genome Sciences Department. Thank you to Daniel Chee for his mentorship, and John Stamatoyannopoulos for the support.

Faculty Advisor: Daniel Chee, Dchee7@altiusinstitute.org

Role: I created scripts which used python modules to find putative distal interactions with miRNA promoters.