INVESTIGATING THE POTENTIAL OF MICRORNA AS REGULATORS OF THE CALPAIN SYSTEM
Author: Joshua Andle
Graduation Year: 2017
Thesis Advisor: Dorothy E. Croall
Description of Publication: Misregulation of the calcium dependent family of proteases known as calpains contributes to several pathologies including Alzheimer’s disease1 and altered cellular functions including regulation of cell cycle2 and the cell motility3. There have not been any investigations into regulation of the calpain system by the newly discovered microRNA (miRNA) system of regulatory molecules. To better understand the regulation of calpains, we have investigated potential interactions of miRNA with five target calpain system members to screen for miRNA interactions possessing a high likelihood of regulating calpain activity. The chosen targets were the catalytic subunits of calpains 1 (CAPN1) and 2 (CAPN2), the small subunit CAPNS1 required for their proper folding, calpain 5 (CAPN5), and the endogenous inhibitor of multiple members of the calpain family, designated calpastatin (CAST). This investigation consisted of 1) manual searching and 2) automated acquisition of miRNA-mRNA interaction data from four databases, as well as a 3) selection of the miRNA interactions with the most supporting evidence. An analysis of all miRNA interaction data was performed for each database to determine trends in miRNA interaction data and to compare the interactions for the calpain system targets to interaction data for all other genes. CAST and CAPNS1 appear to be the most highly targeted by miRNA among the five calpain system members investigated. As regulation of these two targets would affect activity of several members of the calpain family it is of note that they have the most evidence indicating miRNA regulation. Three experiments are proposed to test regulation of CAST and CAPNS1 by hsa-miR-19a, mmu-miR-96, and hsa-miR-124.
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