My research program takes an integrated approach using C. elegans and human cell lines to understand the biological impact of RNA editing. RNA editing is a post-transcriptional modification that alters the nucleotide sequence of RNA from that encoded by the genome. The most prevalent type of editing in humans is adenosine (A) to inosine (I) editing, with ~1,000,000 editing events identified in the human transcriptome. Brain mRNAs, some of which are required for neurogenesis, are the most edited human transcripts, and deletion of the editing machinery in lower organisms, such as C. elegans, results in behavioral defects, indicating RNA editing is required for proper neuronal development and function. In addition, alterations in editing levels have been observed in a number of neuropathological diseases, including epilepsy, depression, amyotrophic lateral sclerosis, and brain tumors. Despite the biological importance of RNA editing, the consequences of editing on normal gene expression and the mechanistic implications of aberrant editing in disease are only beginning to be dissected.
Research in the Hundley lab utilizes a combination of biochemistry, genomics and molecular biology to both charaterize the effects of editing on gene expression and elucidate molecular mechanisms that are important for regulating RNA editing.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 Hundley lab are focused on dissecting the molecular mechanism of this regulator and determining the conservation of this regulatory protein in human cells.