第1221回生物科学セミナー

ncRNA-programmed genome rearrangement in the ciliate Oxytricha

Professor Laura Landweber(Columbia University)

2018年07月13日(金)    15:30-16:30  理学部1号館東棟 287号室   

Piwi-interacing RNAs(piRNAs)help maintain genome integrity in the face of foreign
genomic invaders. The ciliate Oxytricha trifallax is a microbial eukaryote with a scrambled
germline genome. Thousands of RNA-guided genome editing events produce a functional
somatic nucleus during development. Previously, our lab discovered that Otiwi1 associated
piRNAs mark Oxytricha genomic regions for retention during nuclear differentiation.
Here, we report the discovery of a novel class of post-meiotic piRNAs that mark either
germline-limited regions or aberrant structural DNA arrangements that accumulate during
genome remodeling. Unlike-Otiwi-1-associated piRNAs, these post-meiotic piRNAS are
modified by 2’-O-methylation. Biochemical and structural analysis of the Otiwi2 PAZ
domain reveals the basis for specificity of the two PIWI proteins for modified versus
unmodified RNA. Furthermore, injection of synthetic 2’-O-methylated 27nt RNA targeted
against normally retained genomic regions can reprogram the zygote to delete corresponding
regions from the progeny’s somatic genome, and this affect transfers across multiple
generations. Together, these findings underscore the delicate interplay between two nearly
orthogonal classes of piRNAs in maintaining fidelity during the complex process of
programmed genome rearrangement.