Channel nuclear pore complex subunits are required for transposon silencing in


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
15 04 2021
Historique:
received: 07 01 2021
accepted: 14 04 2021
pubmed: 16 4 2021
medline: 27 10 2021
entrez: 15 4 2021
Statut: epublish

Résumé

The nuclear pore complex (NPC) is the principal gateway between nucleus and cytoplasm that enables exchange of macromolecular cargo. Composed of multiple copies of ~30 different nucleoporins (Nups), the NPC acts as a selective portal, interacting with factors which individually license passage of specific cargo classes. Here we show that two Nups of the inner channel, Nup54 and Nup58, are essential for transposon silencing via the PIWI-interacting RNA (piRNA) pathway in the Transposons are genetic sequences, which, when active, can move around the genome and insert themselves into new locations. This can potentially disrupt the information required for cells to work properly: in reproductive organs, for example, transposon activity can lead to infertility. Many organisms therefore have cellular systems that keep transposons in check. Animal cells comprise two main compartments: the nucleus, which contains the genetic information, and the cytosol, where most chemical reactions necessary for life take place. Molecules continually move between nucleus and cytosol, much as people go in and out of a busy train station. The connecting ‘doors’ between the two compartments are called Nuclear Pore Complexes (NPCs), and their job is to ensure that each molecule passing through reaches its correct destination. Recent research shows that the individual proteins making up NPCs (called nucleoporins) may play other roles within the cell. In particular, genetic studies in fruit flies suggested that some nucleoporins help to control transposon activity within the ovary – but how they did this was still unclear. Munafò et al. therefore set out to determine if the nucleoporins were indeed actively silencing the transposons, or if this was just a side effect of altered nuclear-cytosolic transport. Experiments using cells grown from fruit fly ovaries revealed that depleting two specific nucleoporins, Nup54 and Nup58, re-activated transposons with minimal effects on most genes or the overall health of the cells. This suggests that Nup54 and Nup58 play a direct role in transposon silencing. Further, detailed analysis of gene expression in Nup54- and Nup58-lacking cells revealed that the product of one gene,

Autres résumés

Type: plain-language-summary (eng)
Transposons are genetic sequences, which, when active, can move around the genome and insert themselves into new locations. This can potentially disrupt the information required for cells to work properly: in reproductive organs, for example, transposon activity can lead to infertility. Many organisms therefore have cellular systems that keep transposons in check. Animal cells comprise two main compartments: the nucleus, which contains the genetic information, and the cytosol, where most chemical reactions necessary for life take place. Molecules continually move between nucleus and cytosol, much as people go in and out of a busy train station. The connecting ‘doors’ between the two compartments are called Nuclear Pore Complexes (NPCs), and their job is to ensure that each molecule passing through reaches its correct destination. Recent research shows that the individual proteins making up NPCs (called nucleoporins) may play other roles within the cell. In particular, genetic studies in fruit flies suggested that some nucleoporins help to control transposon activity within the ovary – but how they did this was still unclear. Munafò et al. therefore set out to determine if the nucleoporins were indeed actively silencing the transposons, or if this was just a side effect of altered nuclear-cytosolic transport. Experiments using cells grown from fruit fly ovaries revealed that depleting two specific nucleoporins, Nup54 and Nup58, re-activated transposons with minimal effects on most genes or the overall health of the cells. This suggests that Nup54 and Nup58 play a direct role in transposon silencing. Further, detailed analysis of gene expression in Nup54- and Nup58-lacking cells revealed that the product of one gene,

Identifiants

pubmed: 33856346
doi: 10.7554/eLife.66321
pii: 66321
pmc: PMC8133776
doi:
pii:

Substances chimiques

DNA Transposable Elements 0
Drosophila Proteins 0
Nuclear Pore Complex Proteins 0
Nucleocytoplasmic Transport Proteins 0
Nxt1 protein, Drosophila 0
RNA, Long Noncoding 0
RNA, Small Interfering 0
fs(1)Yb protein, Drosophila 0

Banques de données

GEO
['GSE152297']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Cancer Research UK
ID : A21143
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 110161/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom

Informations de copyright

© 2021, Munafò et al.

Déclaration de conflit d'intérêts

MM, VL, AP, SM, SB, IH, MS, GH, BC No competing interests declared

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Auteurs

Marzia Munafò (M)

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

Victoria R Lawless (VR)

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

Alessandro Passera (A)

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

Serena MacMillan (S)

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

Susanne Bornelöv (S)

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

Irmgard U Haussmann (IU)

Department of Life Science, Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, United Kingdom.
School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United Kingdom.

Matthias Soller (M)

School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United Kingdom.
Birmingham Center for Genome Biology, University of Birmingham, Birmingham, United Kingdom.

Gregory J Hannon (GJ)

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

Benjamin Czech (B)

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.

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