The dimeric SFiNX complex enables piRNA-guided co-transcriptional silencing through molecular condensate formation

ABSTRACT: Nuclear Argonaute proteins, guided by their bound small RNAs, orchestrate heterochromatin formation at transposon insertions and repetitive genomic loci. The molecular mechanisms that, besides recruiting heterochromatin effector proteins, are required for this silencing process are poorly understood. Here, we show that the SFiNX complex, the central silencing mediator downstream of nuclear Piwi-piRNA complexes in Drosophila, enables co-transcriptional silencing via the formation of molecular condensates. Condensate formation is stimulated by nucleic acid binding and requires SFiNX to form a homodimer. The dynein light chain dLC8, a highly conserved dimerization hub protein, mediates homo-dimerization of SFiNX. Point mutations preventing dLC8-mediated SFiNX dimerization result in transposon de-repression and sterility. dLC8’s function can be bypassed with a heterologous dimerization domain, suggesting that dimerization is a constitutive rather than a regulated feature of SFiNX. We propose that nucleic-acid stimulated condensate formation enables co-transcriptional silencing through the retention of the target RNA at chromatin, thereby allowing effector proteins to establish heterochromatin at the target locus.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Drosophila Melanogaster (fruit Fly) Mus Musculus (mouse)

TISSUE(S): Ovary, Cell Culture

SUBMITTER: Richard Imre  

LAB HEAD: Julius Brennecke

PROVIDER: PXD022010 | Pride | 2021-02-12

REPOSITORIES: Pride