Chen Laboratory | Yale University

Circular RNAs (circRNAs) are a newly discovered class of RNAs that are generated through back splicing: their 3’ and 5’ ends are joined to form a closed loop. Unlike mRNAs and other linear RNAs, circRNAs lack ends. As a consequence, regulatory elements found on linear RNA, including 5’ caps, 3’ untranslated regions (UTRs), and poly(A) tails are not present on circRNAs. The absence of regulatory features on circRNAs underscores how little is known about these highly-stable RNAs.
Like their linear RNA counterparts, circRNAs exhibit a range of functions within cells. The most notable examples, so far, are as microRNA sponges and as ribosome templates. However, as new circRNA functions continue to be discovered, the regulation of these various functions and their importance in disease remain poorly understood.
We will use a combination of molecular, cellular, genomic, and chemical biology to probe the scope of circRNA function in cells and uncover additional layers of regulation. In particular, we are interested in the movement of circRNAs throughout the cell, their interactions with cellular machinery and metabolites, and regulation of their formation and degradation. We will investigate the impact of RNA secondary structures and post-transcriptional modifications on circRNA function and regulation. Our work will reveal the "life cycle" of circRNAs, establish a cellular atlas of circRNAs, and define the small and macromolecules that contact them. These insights will address a fundamental question in biology of the molecular mechanisms that govern cellular function and provide the platform for developing novel therapies.