Potential role of phase separation in transposon defence

Investigating the role of Spindle-E Zinc Finger motif in piRNA ping-pong biogenesis

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Contact name
Dr Rippei Hayashi

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About

Transposons are relics of past viral infection and constitute 10 to 80% of the eukaryotic genome. Uncontrolled expression of transposons causes DNA damage and sterility, and is associated to cancer progression and inflammatory diseases. We study the small RNA pathway called Piwi-interacting RNA (piRNA) pathway, an evolutionarily conserved defence mechanism against transposons. In the model organism fruit fly Drosophila melanogaster, piRNAs are made from RNA coming from sense and anti-sense strands of transposon via a mechanism called ping-pong.

In an unpublished study, we found that the Zinc Finger motif in the RNA helicase protein Spindle-E is required for efficient piRNA production. Intriguingly, the Spindle-E Zinc Finger resembles those of DNA binding proteins. We hypothesise that the Zinc Finger binds double-stranded RNA from both strands of transposon RNA instead of double-stranded DNA. Furthermore, Spindle-E has an intrinsically disordered region next to the Zinc Finger, which is generally known to contribute to the liquid-liquid phase separation of molecular condensates. In this project, we propose to further investigate the function of Spindle-E Zinc Finger motif in piRNA production and its potential role in phase separation.

The project involves fruit fly genetics, confocal microscopy imaging and next generation sequencing of small RNA.

Members

Supervisor

Rippei Hayashi

Group Leader
Fellow