Understanding how dicer partner proteins establish microRNA target specificity
Karina Jouravleva | Zamore Lab | Charles A. King Trust Postdoctoral Fellowship
MicroRNAs (miRNAs) influence every physiological process, and dysregulated microRNAs have been linked to human diseases, including cancer. MicroRNAs are processed from the double-stranded stem of stem-loop precursor RNAs (pre-miRNAs) by the ribonuclease Dicer. Human Dicer and fly Dicer-1 (Dcr-1) can also process long double-stranded RNA (dsRNA) into small interfering RNAs in vitro, but exclusively make miRNAs in vivo. Moreover, Dicer can process some pre-miRNAs into multiple miRNA isoforms—i.e., isomiRs—whose cellular profiles change dynamically during differentiation and development. Here, I propose single-molecule biochemical and structural studies to answer the following questions:
What restricts Dicer to miRNA processing? How do Dicer partner proteins affect kinetics of miRNA processing? How does Dicer make isomiRs?
