The human genome is littered with small open reading frames (sORFs) encoding very small endogenous peptides, ranging from 20-100 amino acids. These are nestled within non-coding RNAs, pseudogenes and untranslated regions of conventional protein-coding genes and even introns. Such peptides, whose functions are just beginning to be understood, can act as extracellular signaling molecules (such as hormones and cytokines), antimicrobial agents, antigens, or regulatory moieties of larger proteins. Using a combination of bioinformatics, proteomics and next-generation sequencing, we are systematically defining these endogenous peptides and uncovering their functions, focusing on the cardiovascular system, which is well known for employing peptide hormones to effect homeostatic control (e.g. ANPs, Angiotensin, Apelin etc). We are also interested in the functional and structural relationships between RNAs and their resident sORFs, with the hypothesis that sORF-containing RNAs toggle between coding and non-coding states. sORF translation therefore modulates (non-coding) RNA activity, and vice versa. We are interested in elucidating the mechanisms underlying such toggling.
For more information, please contact Lena Ho