My research focuses on the discovery and characterization of small functional peptides encoded by long noncoding RNA. Emphasis is placed on peptides that could have implications in breast and prostate cancer development and outcomes. This involves both computational analysis and experimental validation. Broadly, I am interested in increasing understanding of human genetics to improve disease treatment. I am in the Human and Statistical Genetics PhD program at Washington University and received my undergraduate degree from University of Missouri.
Emily Coonrod, Ghofran Othoum, Andrew Nickless, Jin Zhang, Matthew Inkman, Sidi Zhao, Ha Dang, Jace Webster, Emily Rozycki, Sherron Fontes, Nicole White, Christopher Maher
Washington University, St. Louis, MO, USA
Long noncoding RNAs (lncRNAs) have biological and clinical significance in cancer, but their mechanisms remain underexplored. One emerging mechanism includes translation of small peptides with reported roles in cancer progression from annotated lncRNAs, highlighting the need for efficient mechanism prediction and validation of specific candidates. Through comprehensive proteogenomic analysis, we found several additional well-known oncogenic lncRNAs and uncharacterized, cancer type-specific lncRNAs with support for peptide coding capabilities. Our pipeline combined conservation, protein prediction, and mass spectrometry support to produce a catalog of potential peptides more refined than previous studies considering fewer avenues of support. LncRNAs with highest support, including H19, PCAT19, and NR2F1-AS1 are described in PepTransDB (Peptide Encoding Transcripts Database). We chose two well-known candidates in breast cancer to validate experimentally, as breast cancer is the second most common cancer among women in the United States, and around 43,000 women die from breast cancer each year. The first candidate, HOTAIR, is implicated in breast cancer progression and survival and in many other cancer types. Translation of a peptide from HOTAIR was experimentally confirmed in breast cancer cell lines though overexpression of a FLAG-tagged construct. A translated peptide was similarly confirmed from a second candidate, BCAR4, which preliminary data indicate is functional in breast cancer. Our study will expand the understanding of lncRNA coding potential and regulatory mechanisms in RNA biology and refine the landscape of lncRNAs with coding potential in breast cancer.