"Panoramix：the missing link between the piRNA pathway and general silencing machinery" Dr. Yang Yu

Dr. Yang Yu
Postdoc Fellow
Cold Spring Harbor Laboratory

 

Abstract

The Piwi-interacting RNA (piRNA) pathway is a small RNA-based innate immune system that defends germ
cell genomes against parasidic transposons. In Drosophila ovaries, the nuclear Piwi protein is required for
transcriptional silencing of transposons, though the precise mechanisms by which this occurs are unknown.
To address these questions, we took advantage of a λN/BoxB tethering system to mimic piRNA targeting.
Surprisingly, artificial tethering of λN-Piwi to a luciferase reporter containing BoxB sites failed to silence
the expression of the reporter. In contrast, Piwi can silence its target if guided via artificial piRNAs.
Therefore, conformation changes and/or additional cofactors may be required to activate Piwi:piRNA RISC
complexes to silence their targets.

Through mining the data from several independent genome-wide RNAi screens for factors required for
transposon silencing, we identified an ovary specific nuclear protein (CG9754/Panoramix) that can
influence global transposon transcription similarly as Piwi when eliminated. The effect is not due to the
defects of piRNA biogenesis since levels of piRNAs remained unchanged and Piwi proteins stayed bound
with piRNAs in nucleus. Strikingly, enforced tethering of this protein to nascent mRNA transcripts causes
co-transcriptional silencing of the source locus (~1000 fold repression) and the deposition of repressive
chromatin marks. Interestingly, this protein is a component of Piwi complexes that functions downstream of
Piwi and its binding partner, Asterix. We have named this gene Panoramix, the mentor who empowers
Asterix to perform his feats of strength. Importantly, we found that both Eggless/dSetDB1 (H3K9
methyltransferase) and dLSD1 (H3K4me2 demethylase) are required for Panoramix-mediated silencing.
Therefore, we propose that Panoramix forms one of the missing links between the piRNA pathway and the
general silencing machinery that it recruits to enforce transcriptional repression to protect germline from
deleterious transposons.

Biography

Yu, Yang, PhD, graduated with Bachelor degree in Virology from Wuhan University in 2002. Then he came
to United Stated to pursue graduate study under the guidance of Dr. Timohty Nilsen, director of the Center
for RNA Molecular Biology at Case Western Reserve Univesity. In 2007, he obtained PhD degree in
Biochemistry from CWRU and stayed in the same lab for a short postdoc. Since 2010, he has been working
in Dr. Gregory Hannon’s lab at Cold Spring Harbor Laboratory as post-doc fellow. During PhD, Dr. Yu
focused on understanding the mechanism of alternative splicing in mammalian cells and published a first
author paper in Cell. During his postdoc, he mainly focused on dissecting the mechanism of piRNAmediated
transcriptional silencing. He recently published a first author Science paper describing the
missing link between the piRNA pathway and the general transcriptional silencing machinery, which he
named Panoramix, a character from the French comic book. Meanwhile, in collaboration of another postdoc
in Hannon lab, they also discovered an essential gene required for piRNA biogenesis using forward
genetics and published the story in RNA. Interestingly, this gene mainly localized to the outer membrane of
mitochondria and they later named this gene as Minotaur.