The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation
| Autor: | Julia Batki, Karl Mechtler, Veselin I. Andreev, Dominik Handler, Maria Novatchkova, Kotryna Kauneckaite, Julius Brennecke, Lisa Lampersberger, Christian E. Stieger, Jakob Schnabl, Dinshaw J. Patel, Juncheng Wang, Wei Xie |
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| Rok vydání: | 2019 |
| Předmět: |
Transposable element
Models Molecular Small RNA Nucleocytoplasmic Transport Proteins endocrine system Transcription Genetic Protein Conformation Heterochromatin Genome Insect Piwi-interacting RNA RNA transport RNA-binding protein Biology Crystallography X-Ray Article 03 medical and health sciences 0302 clinical medicine Structural Biology Protein Interaction Mapping Animals Drosophila Proteins Gene silencing Amino Acid Sequence Gene Silencing RNA Small Interfering Nuclear export signal Molecular Biology 030304 developmental biology 0303 health sciences Messenger RNA Binding Sites Sequence Homology Amino Acid urogenital system Nuclear Proteins RNA-Binding Proteins RNA Cell biology Drosophila melanogaster Gene Expression Regulation Multiprotein Complexes Argonaute Proteins DNA Transposable Elements Protein Multimerization Sequence Alignment 030217 neurology & neurosurgery |
| Zdroj: | Nature Structural & Molecular Biology Nature structural & molecular biology |
| ISSN: | 1545-9993 |
| DOI: | 10.1038/s41594-019-0270-6 |
| Popis: | The PIWI-interacting RNA (piRNA) pathway protects genome integrity in part through establishing repressive heterochromatin at transposon loci. Silencing requires piRNA-guided targeting of nuclear PIWI proteins to nascent transposon transcripts, yet the subsequent molecular events are not understood. Here, we identify SFiNX (silencing factor interacting nuclear export variant), an interdependent protein complex required for Piwi-mediated cotranscriptional silencing in Drosophila. SFiNX consists of Nxf2–Nxt1, a gonad-specific variant of the heterodimeric messenger RNA export receptor Nxf1–Nxt1 and the Piwi-associated protein Panoramix. SFiNX mutant flies are sterile and exhibit transposon derepression because piRNA-loaded Piwi is unable to establish heterochromatin. Within SFiNX, Panoramix recruits heterochromatin effectors, while the RNA binding protein Nxf2 licenses cotranscriptional silencing. Our data reveal how Nxf2 might have evolved from an RNA transport receptor into a cotranscriptional silencing factor. Thus, NXF variants, which are abundant in metazoans, can have diverse molecular functions and might have been coopted for host genome defense more broadly. Identification of SFiNX, a complex of Nxf2–Nxt1, a variant of the mRNA export receptor Nxf1–Nxt1 and the Piwi-associated protein Panoramix, demonstrates an RNA export independent role for Nxf2 in piRNA-guided cotranscriptional transposon silencing. |
| Databáze: | OpenAIRE |
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