Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex

Schnabl, Jakob; Wang, Juncheng; Hohmann, Ulrich; Gehre, Maja; Batki, Julia; Andreev, Veselin I.; Purkhauser, Kim; Fasching, Nina; Duchek, Peter; Novatchkova, Maria; Mechtler, Karl; Plaschka, Clemens; Patel, Dinshaw J.; Brennecke, Julius

doi:10.1101/gad.347989.120

Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex

Journal Article · Thu Feb 11 00:00:00 EST 2021 · Genes & Development

DOI:https://doi.org/10.1101/gad.347989.120· OSTI ID:1829866

Schnabl, Jakob ^[1]; Wang, Juncheng ^[2]; Hohmann, Ulrich ^[3]; Gehre, Maja ^[4]; Batki, Julia ^[4]; Andreev, Veselin I. ^[1]; Purkhauser, Kim ^[4]; Fasching, Nina ^[4]; Duchek, Peter ^[4]; Novatchkova, Maria ^[4]; ^[5]; Plaschka, Clemens ^[5]; Patel, Dinshaw J. ^[2]; ^[4]

Inst. of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna (Austria); Doctoral School at the Univ. of Vienna and Medical Univ. of Vienna (Austria)
Memorial Sloan Kettering Cancer Center, New York, NY (United States)
Inst. of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna (Austria); Research Inst. of Molecular Pathology (IMP), Vienna (Austria)
Inst. of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna (Austria)
Research Inst. of Molecular Pathology (IMP), Vienna (Austria)

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: NIH; USDOE; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1829866

Alternate ID(s):: OSTI ID: 1834935

Journal Information:: Genes & Development, Journal Name: Genes & Development Journal Issue: 5-6 Vol. 35; ISSN 0890-9369

Publisher:: Cold Springs Harbor Laboratory PressCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
Drosophila oogenesis
LC8
Panoramix
Piwi
cotranscriptional silencing
heterochromatin formation
molecular condensates
piRNA pathway
transposon silencing

Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex

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References (72)

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