Heather A. HundleyAssistant Professor, Medical Science
Office: Jordan Hall 213
Ph.D., University of Wisconsin, 2005
Helen Hay Whitney Postdoctoral Fellow, University of Utah, 2005-2009
Dr. Hundley is interested in post-transcriptional mechanisms of regulating gene expression. 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. The 3’ untranslated region (3’ UTR) of mRNAs is a “hotspot” for regulatory elements that direct post-transcriptional gene regulation. My lab is currently focusing on how long double-stranded structures present in 3’ UTRs affect gene expression both in human cell lines and in the microscopic worm, Caenorhabditis elegans.
Double-stranded RNA (dsRNA) structures are present in over 5% of human protein coding genes. These regions are targets of the Adenosine deaminase that act on RNA (ADAR) family of enzymes. ADARs bind to dsRNA and catalyze a hydrolytic deamination of adenosine to result in inosine-a process is referred to as RNA editing. Alterations in editing occur in a number of diseases, including epilepsy, schizophrenia, amyotrophic lateral sclerosis, and many types of cancer. Despite their biological importance, the role of ADARs in regulating gene expression is unclear.
Our main goals are to determine the mechanism of how double-stranded structures, and the inosines within them, affect gene expression and elucidate the biological function of ADARs. We use a combination of biochemistry, genetics, and molecular and cellular biology in both worm and human systems to identify the cellular factors and conditions that allow RNA structures and ADARs to regulate gene expression.
Deffit SN and Hundley HA (2015) To edit or not to edit: regulation of ADAR editing specificity and efficiency, Wiley Interdisciplinary Reviews RNA, 2015 Nov 26. doi: 10.1002/wrna.1319.
Wheeler EC, Washburn MC, Major F, Rusch DB, Hundley HA (2015) Noncoding regions of C. elegans mRNA undergo selective adenosine to inosine deamination and contain a small number of editing sites per transcript, RNA Biology, 2015 Feb;12(2):162-74. doi:10.1080/15476286.2015.1017220.
Washburn MC and Hundley HA (in press) Controlling the editor: the many roles of RNA binding proteins in regulating A-to-I RNA editing, in RNA processing: disease and genome-wide probing, G. Yeo ed. (Springer Press)
Washburn MC, Kakaradov B, Sundararaman B, Wheeler E, Hoon S, Yeo GW, Hundley HA (2014) The dsRBP and Inactive Editor, ADR-1, Utilizes dsRNA Binding to Regulate A-to-I RNA Editing across the C. elegans Transcriptome, Cell Reports, 2014 Feb 4; pii: S2211-1247(14)00028-X
- IU Press Release: http://news.indiana.edu/releases/iu/2014/02/hundley-messenger-rna.shtml
- Featured on the NSF website News from the Field: http://www.nsf.gov/news/news_summ.jsp?cntn_id=130446&org=NSF&from=news
Hundley HA (2013) Regulation of gene expression through inosine-containing UTRs, In RNA Editing: Current Research and Future Trends, S. Maas, ed. (Horizon Press )
Bass B, Hundley H, Li JB, Peng Z, Pickrell J, Xiao XG, Yang L. (2012) The difficult calls in RNA editing, Nature Biotechnology, 2012 Dec 7;30(12):1207-9.
Capshew CR, Dusenbury KL and Hundley HA (2012) Inverted Alu dsRNA structures do not affect localization but can alter translation efficiency of human mRNAs independent of RNA editing, Nucleic Acids Res., 2012 Sep 1;40(17):8637-8645.
Hundley HA and Bass BL (2010) ADAR editing in double-stranded UTRs and other noncoding RNA sequences, TIBS, 2010 Jul;35(7):377-383.
Hundley HA, Krauchuk AA, Bass BL (2008) C. elegans and H. sapiens mRNAs with edited 3’ UTRs are present on polysomes, RNA, 2008 Oct;14(10):2050-2060.
Bass BL, Hellwig S, Hundley HA. (2005) A nuclear RNA is cut out for Translation, Cell, 2005 Oct21;123(2):181-183.
Hundley HA, Walter W, Bairstow S, Craig, EA. (2005) Human Mpp11 J-protein: Ribosome- tethered Molecular Chaperones Are Ubiquitous, Science, 2005 May 13; 308(5724):1032-4. (Science Express 2005 Mar 31).
Hundley H, Eisenman H, Walter W, Evans T, Hotokezaka Y, Wiedmann M, Craig E. (2002) The in vivo function of the ribosome-associated Hsp70, Ssz1, does not require its putative peptide-binding domain. Proc. Natl. Acad. Sci., 2002 Apr 2;99(7):4203-8.