Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex Journal Article
| Authors: | Schnabl, J.; Wang, J.; Hohmann, U.; Gehre, M.; Batki, J.; Andreev, V. I.; Purkhauser, K.; Fasching, N.; Duchek, P.; Novatchkova, M.; Mechtler, K.; Plaschka, C.; Patel, D. J.; Brennecke, J. |
| Article Title: | Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex |
| Abstract: | Nuclear Argonaute proteins, guided by their bound small RNAs to nascent target transcripts, mediate cotranscriptional silencing of transposons and repetitive genomic loci through heterochromatin formation. The molecular mechanisms involved in this process are incompletely understood. Here, we show that the SFiNX complex, a silencing mediator downstream from nuclear Piwi-piRNA complexes in Drosophila, facilitates cotranscriptional silencing as a homodimer. The dynein light chain protein Cut up/LC8 mediates SFiNX dimerization, and its function can be bypassed by a heterologous dimerization domain, arguing for a constitutive SFiNX dimer. Dimeric, but not monomeric SFiNX, is capable of forming molecular condensates in a nucleic acid-stimulated manner. Mutations that prevent SFiNX dimerization result in loss of condensate formation in vitro and the inability of Piwi to initiate heterochromatin formation and silence transposons in vivo. We propose that multivalent SFiNX-nucleic acid interactions are critical for heterochromatin establishment at piRNA target loci in a cotranscriptional manner. © 2021 Schnabl et al.; Published by Cold Spring Harbor Laboratory Press. |
| Keywords: | piwi; pirna pathway; heterochromatin formation; drosophila oogenesis; cotranscriptional silencing; lc8; molecular condensates; panoramix; transposon silencing |
| Journal Title: | Genes and Development |
| Volume: | 35 |
| Issue: | 5-6 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2021-03-01 |
| Start Page: | 392 |
| End Page: | 409 |
| Language: | English |
| DOI: | 10.1101/gad.347989.120 |
| PUBMED: | 33574069 |
| PROVIDER: | scopus |
| PMCID: | PMC7919418 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2021 -- Source: Scopus |
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