第1181回生物科学セミナー

Mechanisms to define and tune the length of small silencing RNAs

福永流也博士(Johns Hopkins University School of Medicine)

2017年12月28日(Thu)    14:00-15:00  理学部3号館 326号室   

MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are produced by the multi-domain Dicer enzymes. miRNAs mainly regulate endogenous gene expression, while siRNAs silence transposons and viruses. miRNAs and siRNAs must have a correct length for their proper functions. miRNAs and siRNAs with an incorrect length can cause detrimental effects in cells, because they have altered seed sequence and target repertoire compared with the small RNAs with a correct length and/or because they cannot be bound by an appropriate effector protein Argonaute. Small RNAs with an incorrect length are produced if Dicer selects incorrect cleavage sites in precursor RNAs. Thus, understanding the molecular mechanisms by which the length of small RNAs produced by Dicer is defined and regulated is significant.
In Drosophila, Dicer-1 produces ~21-24 nt miRNAs from pre-miRNAs while Dicer-2 precisely produces 21 nt siRNAs from long dsRNAs derived from viruses and transposons. In the first topic, I will present our project to understand the molecular mechanism by which Dicer-2 produces 21 nt siRNAs with a remarkably high length fidelity. In the second topic, I will present our project to understand the molecular mechanism by which Dicer partner proteins (Loquacious-PB in Drosophila and TRBP in mammals) change the length of miRNAs produced by Dicer enzymes, contributing to the production of alternative isoforms of miRNAs called isomiRs that have altered length.