Indiana University

IU-MSI STEM Initiative

Heather Hundley

www.hundleylab.org

My lab is trying to understand the impact of double-stranded RNA and RNA editing on post-transcriptional regulation of gene expression in both normal and cancerous cells. We use a combination of biochemistry, genomics/genetics and molecular biology in both the model organism Caenorhabditis elegans (microscopic worms) and human cell lines to address our questions.

Proper control of gene expression is critical for the normal development of all organisms. Errors in regulating mRNA (post-transcriptional gene expression) account for over 20% of all human genetic diseases, including many types of cancer. Post-transcriptional gene regulation is governed by the interactions of trans-acting factors with cis-acting elements, which are typically found within the noncoding or untranslated regions (UTRs) of mRNA. Our lab is interested in understanding how a family of proteins called ADARs recognize and modifies double-stranded regions within UTRs to regulate gene expression.

ADARs are highly expressed in the nervous system of both worms and humans. ADARs bind to double-stranded RNA (dsRNA) and convert adenosine (A) to inosine (I), a process called RNA editing. Current estimates predict over 1 million A-to-I editing events in noncoding regions of the human transcriptome. Global hypoediting of these events has been reported in many neuropathological diseases, including epilepsy, schizophrenia, amyotrophic lateral sclerosis, and many types of cancer, including glioblastomas (brain tumors). However the levels of the ADAR proteins are not altered in disease, implying that other mechanisms to regulate ADAR-mediated RNA editing exist. We have recently utilized next generation sequencing and molecular biology approaches to identify a major regulator of noncoding editing in C. elegans. Current efforts in the lab are focused on dissecting the regulatory mechanism and determining the conservation of this regulatory protein in human cells.

Revised: Oct. 4, 2015

Sarah Larson
Program Coordinator
IU-MSI STEM Initiative
Indiana University
set9@indiana.edu
812-855-7463