Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila

In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panor...

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Main Authors: Evelyn L Eastwood, Kayla A Jara, Susanne Bornelöv, Marzia Munafò, Vasileios Frantzis, Emma Kneuss, Elisar J Barbar, Benjamin Czech, Gregory J Hannon
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-02-01
Series:eLife
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Online Access:https://elifesciences.org/articles/65557
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author Evelyn L Eastwood
Kayla A Jara
Susanne Bornelöv
Marzia Munafò
Vasileios Frantzis
Emma Kneuss
Elisar J Barbar
Benjamin Czech
Gregory J Hannon
author_facet Evelyn L Eastwood
Kayla A Jara
Susanne Bornelöv
Marzia Munafò
Vasileios Frantzis
Emma Kneuss
Elisar J Barbar
Benjamin Czech
Gregory J Hannon
author_sort Evelyn L Eastwood
collection DOAJ
description In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panoramix-induced co-transcriptional silencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Loss of Ctp results in transposon de-repression and a reduction in repressive chromatin marks specifically at transposon loci. In turn, Ctp can enforce transcriptional silencing when artificially recruited to RNA and DNA reporters. We show that Ctp drives dimerisation of the PICTS complex through its interaction with conserved motifs within Panoramix. Artificial dimerisation of Panoramix bypasses the necessity for its interaction with Ctp, demonstrating that conscription of a protein from a ubiquitous cellular machinery has fulfilled a fundamental requirement for a transposon silencing complex.
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spelling doaj.art-8c72a5d9b9b2465db0cee631acd9807f2022-12-22T03:33:48ZengeLife Sciences Publications LtdeLife2050-084X2021-02-011010.7554/eLife.65557Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in DrosophilaEvelyn L Eastwood0https://orcid.org/0000-0002-3932-0402Kayla A Jara1https://orcid.org/0000-0003-0406-2957Susanne Bornelöv2https://orcid.org/0000-0001-9276-9981Marzia Munafò3https://orcid.org/0000-0002-2689-8432Vasileios Frantzis4https://orcid.org/0000-0002-3497-700XEmma Kneuss5https://orcid.org/0000-0003-0662-8539Elisar J Barbar6https://orcid.org/0000-0003-4892-5259Benjamin Czech7https://orcid.org/0000-0001-8471-0007Gregory J Hannon8https://orcid.org/0000-0003-4021-3898Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomDepartment of Biochemistry and Biophysics, Oregon State University, Corvallis, United StatesCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomDepartment of Biochemistry and Biophysics, Oregon State University, Corvallis, United StatesCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United KingdomIn animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panoramix-induced co-transcriptional silencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Loss of Ctp results in transposon de-repression and a reduction in repressive chromatin marks specifically at transposon loci. In turn, Ctp can enforce transcriptional silencing when artificially recruited to RNA and DNA reporters. We show that Ctp drives dimerisation of the PICTS complex through its interaction with conserved motifs within Panoramix. Artificial dimerisation of Panoramix bypasses the necessity for its interaction with Ctp, demonstrating that conscription of a protein from a ubiquitous cellular machinery has fulfilled a fundamental requirement for a transposon silencing complex.https://elifesciences.org/articles/65557piRNA pathwayco-transcriptional silencingtransposonheterochromatindimerisationLC8
spellingShingle Evelyn L Eastwood
Kayla A Jara
Susanne Bornelöv
Marzia Munafò
Vasileios Frantzis
Emma Kneuss
Elisar J Barbar
Benjamin Czech
Gregory J Hannon
Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
eLife
piRNA pathway
co-transcriptional silencing
transposon
heterochromatin
dimerisation
LC8
title Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
title_full Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
title_fullStr Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
title_full_unstemmed Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
title_short Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
title_sort dimerisation of the picts complex via lc8 cut up drives co transcriptional transposon silencing in drosophila
topic piRNA pathway
co-transcriptional silencing
transposon
heterochromatin
dimerisation
LC8
url https://elifesciences.org/articles/65557
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