Proteopedia

6opf

Crystal structure of dmNxf2 UBA domain fused with Panoramix helixCrystal structure of dmNxf2 UBA domain fused with Panoramix helix

Structural highlights

6opf is a 4 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NXF2_DROME May be involved in the export of mRNA from the nucleus to the cytoplasm.[1] PANX_DROME Acts via the piwi-interacting RNA (piRNA) pathway which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and piwi proteins and governs the methylation and subsequent repression of transposons (PubMed:26472911, PubMed:26494711). Required for transcriptional silencing of transposons targeted by piwi and confers its effects by interacting with nascent RNA transcripts (PubMed:26472911, PubMed:26494711). Likely to be recruited to nascent transcripts cotranscriptionally by piwi and to recruit additional factors involved in transcriptional silencing (PubMed:26472911). In the ovaries, forms a complex with nxf2, piwi and Nxt1 which acts as effectors of cotranscriptional transposon silencing (PubMed:31219034, PubMed:31368590, PubMed:31570835, PubMed:31384064). The interaction with nxf2 stabilizes the nuclear protein complex (PubMed:31384064).[2] [3] [4] [5] [6] [7]

Publication Abstract from PubMed

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.

The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation.,Batki J, Schnabl J, Wang J, Handler D, Andreev VI, Stieger CE, Novatchkova M, Lampersberger L, Kauneckaite K, Xie W, Mechtler K, Patel DJ, Brennecke J Nat Struct Mol Biol. 2019 Aug;26(8):720-731. doi: 10.1038/s41594-019-0270-6. Epub, 2019 Aug 5. PMID:31384064[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Herold A, Klymenko T, Izaurralde E. NXF1/p15 heterodimers are essential for mRNA nuclear export in Drosophila. RNA. 2001 Dec;7(12):1768-80. PMID:11780633
  2. ↑ Yu Y, Gu J, Jin Y, Luo Y, Preall JB, Ma J, Czech B, Hannon GJ. Panoramix enforces piRNA-dependent cotranscriptional silencing. Science. 2015 Oct 16;350(6258):339-42. PMID:26472911 doi:10.1126/science.aab0700
  3. ↑ Sienski G, Batki J, Senti KA, Dönertas D, Tirian L, Meixner K, Brennecke J. Silencio/CG9754 connects the Piwi-piRNA complex to the cellular heterochromatin machinery. Genes Dev. 2015 Nov 1;29(21):2258-71. PMID:26494711 doi:10.1101/gad.271908.115
  4. ↑ Fabry MH, Ciabrelli F, Munafò M, Eastwood EL, Kneuss E, Falciatori I, Falconio FA, Hannon GJ, Czech B. piRNA-guided co-transcriptional silencing coopts nuclear export factors. Elife. 2019 Jun 20;8:e47999. PMID:31219034 doi:10.7554/eLife.47999
  5. ↑ Murano K, Iwasaki YW, Ishizu H, Mashiko A, Shibuya A, Kondo S, Adachi S, Suzuki S, Saito K, Natsume T, Siomi MC, Siomi H. Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing. EMBO J. 2019 Sep 2;38(17):e102870. PMID:31368590 doi:10.15252/embj.2019102870
  6. ↑ Batki J, Schnabl J, Wang J, Handler D, Andreev VI, Stieger CE, Novatchkova M, Lampersberger L, Kauneckaite K, Xie W, Mechtler K, Patel DJ, Brennecke J. The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation. Nat Struct Mol Biol. 2019 Aug;26(8):720-731. doi: 10.1038/s41594-019-0270-6. Epub, 2019 Aug 5. PMID:31384064 doi:http://dx.doi.org/10.1038/s41594-019-0270-6
  7. ↑ Zhao K, Cheng S, Miao N, Xu P, Lu X, Zhang Y, Wang M, Ouyang X, Yuan X, Liu W, Lu X, Zhou P, Gu J, Zhang Y, Qiu D, Jin Z, Su C, Peng C, Wang JH, Dong MQ, Wan Y, Ma J, Cheng H, Huang Y, Yu Y. A Pandas complex adapted for piRNA-guided transcriptional silencing and heterochromatin formation. Nat Cell Biol. 2019 Oct;21(10):1261-1272. doi: 10.1038/s41556-019-0396-0. Epub, 2019 Sep 30. PMID:31570835 doi:http://dx.doi.org/10.1038/s41556-019-0396-0
  8. ↑ Batki J, Schnabl J, Wang J, Handler D, Andreev VI, Stieger CE, Novatchkova M, Lampersberger L, Kauneckaite K, Xie W, Mechtler K, Patel DJ, Brennecke J. The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation. Nat Struct Mol Biol. 2019 Aug;26(8):720-731. doi: 10.1038/s41594-019-0270-6. Epub, 2019 Aug 5. PMID:31384064 doi:http://dx.doi.org/10.1038/s41594-019-0270-6

6opf, resolution 2.00Å

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