Characterizing functional translation in putative 'noncoding' regions of a genome

It is fundamentally important to understand how functional information is encoded by a genome. Characterizing these functional elements can bring novel mechanistic insights into biological processes ranging from normal development to disease progression. I developed a computational algorithm to analyze ribosome profiling data, and unexpectedly revealed thousands of short open reading frames (sORFs) encoded by putative ‘noncoding’ regons, including lncRNAs, pseudogenes and 5’UTRs in a cell. Some of the sORFs are conserved during evolution, suggesting biological importance. My study together with several other genetic studies in model species opened a new research frontier to study the biological roles of sORFs encoded in a genome. Here I propose combined experimental and computational genomics approaches to systematically characterize biological functions of sORFs. First, we will study evolutionary principles of sORF during eukaryotic evolution from yeast to human. Second, we will study the stability and degradation pathways of short peptides using ORFeome and mass spectrometry. Third, we will examine the importance of sORFs on cell proliferation using CRISPR screening. Finally, we will study the functional roles of sORFs regulating RNA stability. Taken together, our study will shed the light on the functional characterization of newly-identified translated regions in a genome and provide new insights into the basic principles of genomic coding. Our findings will have far-reaching implications for the molecular understanding of RNA translation and peptide functions underlying development and diseases.