Selective effects of miRNA effector protein Argonaute on miRNA processing

Since the discovery of miRNAs, studies have been focused on understanding the mechanisms of miRNA biogenesis. However, the molecular/mechanistic function of some miRNA biogenesis factors remain elusive. This project examines a novel role for Argonaute proteins as a factor in regulation of the pre-mir-124 hairpin. Pre-miR-124, but not other pre-miRNAs, was reduced in response to Ago overexpression. This phenomenon was reproducible in mouse and fly cells, suggesting that the mechanism is broadly conserved. Ago-dependent decrease of pre-miR-124 was shown not to be caused by secondary effects of miR-124 target regulation. Experiments using Dicer knockout cells revealed that Ago-induced reduction of pre-mir-124 is a Dicer-dependent phenomenon. Overexpression of Ago2 appeared to result in an increase in the average neurite length of N2a cells. These observations suggest previously unknown roles for the core miRNA biogenesis factors.Doctor of Philosoph