Poster abstracts
Poster number 132 submitted by Emily Slobodenyuk
Identifying the role of 3’UTRs in transcriptional regulation of the calmodulin gene family
Emily Slobodenyuk (Cellular and Molecular Biology Program, University of Michigan), Brittany Bowman (Department of Biological Chemistry, University of Michigan), Chase Weidmann (Department of Biological Chemistry, University of Michigan)
Abstract:
Calmodulin (CaM) is an essential, highly conserved, ubiquitously expressed calcium-binding protein, and interacts with many proteins to regulate a myriad of cellular functions, including the cell cycle, cell motility, and the regulation of ion channels. Due to calmodulin’s importance, mutations in the calmodulin gene or misregulation of the protein contributes to cancer, heart disease, and neurological disorders. Interestingly, in mammals, three CaM genes at three separate autosomal loci express divergent mRNA (CALM1, CALM2, CALM3) that each encode an identical calmodulin protein. Expression of CaM varies in different tissues, variants localize in unique patterns, and mutations in each CaM gene yield distinct phenotypes. The idea of unique transcript roles is further supported by evolutionary conservation, as there is a higher degree of conservation of CaM variants between species than between the CaM variants within each species, especially in their 3′UTRs. Therefore, we hypothesize that sequences within the 3′UTRs govern mRNA localization, with local translation of the transcripts determining the subcellular localization of CaM protein, and thus, unique signaling responses. We will the determine the contribution of each transcript to the total protein and determine if there are transcript-specific protein compartments using RNA FISH and immunofluorescent tagging of each protein. We will determine the cis-regulatory elements necessary for the localization of the transcripts by chemical probing and genetic screening/ We hope to better understand the transcript-level regulation of CaM genes, with the resulting knowledge being broadly applicable to other RNAs.
References:
Kahl et al., Endocr Rev., 2003
Villalobo, et al. Int J Mol Sci, 2020
Wu et al., Int J Mol Sci, 2021
Beghi et al. , Int J Mol Sci, 2022
O’Day et al., Int J Mol Sci, 2020
Gnegy et al., Brain Res, 1991
Munk et al., Cell Calcium, 2022
Toutenhoofd, et al., Cell Calcium, 2000
Palfi et al., J Histochem Cytochem, 1999
Palfi et al., Life Sci., 2002
Zhang et al., Neurosci., 1993
Bogdanov et al., Biophys J., 2022
Bogdanov et al., Biophys J., 2024
Fischer et al., J Biol Chem., 1988
Keywords: 3UTRs, mRNA localization