To export, or not to export: how nuclear export factor variants resolve Piwi's dilemma

Author(s):  
Sheng Wang ◽  
Xiaohua Lu ◽  
Ding Qiu ◽  
Yang Yu

Piwi-interacting RNAs (piRNAs) defend animal gonads by guiding PIWI-clade Argonaute proteins to silence transposons. The nuclear Piwi/piRNA complexes confer transcriptional repression of transposons, which is accompanied with heterochromatin formation at target loci. On the other hand, piRNA clusters, genomic loci that transcribe piRNA precursors composed of transposon fragments, are often recognized by piRNAs to define their heterochromatic identity. Therefore, Piwi/piRNA complexes must resolve this conundrum of silencing transposons while allowing the expression of piRNA precursors, at least in Drosophila germlines. This review is focused on recent advances how the piRNA pathway deals with this genetic conflict.

2019 ◽  
Author(s):  
Julia Batki ◽  
Jakob Schnabl ◽  
Juncheng Wang ◽  
Dominik Handler ◽  
Veselin I. Andreev ◽  
...  

ABSTRACTThe PIWI-interacting RNA (piRNA) pathway protects animal 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 co-transcriptional silencing in Drosophila. SFiNX consists of Nxf2-Nxt1, a gonad-specific variant of the heterodimeric mRNA export receptor Nxf1-Nxt1, and the Piwi-associated protein Panoramix. SFiNX mutant flies are sterile and exhibit transposon de-repression because piRNA-loaded Piwi is unable to establish heterochromatin. Within SFiNX, Panoramix recruits the heterochromatin effectors, while the RNA binding Nxf2 protein licenses co-transcriptional silencing. Our data reveal how Nxf2 evolved from an RNA transport receptor into a co-transcriptional silencing factor. Thus, NXF-variants, which are abundant in metazoans, can have diverse molecular functions and might have been co-opted for host genome defense more broadly.


Philosophy ◽  
1933 ◽  
Vol 8 (29) ◽  
pp. 14-29 ◽  
Author(s):  
F. A. Lindemann

Recent advances in physics render a reconsideration of the Place of Mathematics in the Interpretation of the Universe particularly timely. On the one hand, we have the introduction of non-euclidian geometry, which has given rise to much controversy informed or otherwise; on the other hand, we find mysterious forms of mathematics, invented to cope with the quantum difficulties, which so far have escaped metaphysical investigation or criticism. It would seem most desirable that these modes of interpreting reality should be examined from the broader philosophical point of view.


Synthesis ◽  
2020 ◽  
Vol 52 (19) ◽  
pp. 2731-2760
Author(s):  
Egle M. Beccalli ◽  
Michael S. Christodoulou ◽  
Francesca Foschi ◽  
Sabrina Giofrè

Palladium-catalyzed domino reactions are advanced tools in achieving various nitrogen-containing heterocycles in an efficient and economical manner due to the reduced number of steps in the process. This review highlights recent advances in domino processes aimed at the synthesis of indole derivatives and polycyclic systems containing the indole nucleus in intra/intra- or intra/intermolecular reactions. In particular, we consider domino processes that involve a double bond in a step of the sequence, which allow the issue of regioselectivity in the cyclization to be faced and overcome. The different sections in this review focus on the synthesis of the indole nucleus and functionalization of the scaffold starting from different substrates that have been identified as activated starting materials, which involve a halogenated moiety or unactivated unsaturated systems. In the former case, the reaction is under Pd(0) catalysis, and in the second case a Pd(II) catalytic species is required and then an oxidant is necessary to reconvert the Pd(0) into the active Pd(II) species. On the other hand, the second method has the advantage that it uses easy available and inexpensive substrates.1 Introduction2 Indole Scaffold Synthesis2.1 Activated Substrates2.2 Unactivated Substrates3 Functionalization of Indole Scaffold3.1 Activated Substrates3.2 Unactivated Substrates4 Conclusions


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Martin H Fabry ◽  
Filippo Ciabrelli ◽  
Marzia Munafò ◽  
Evelyn L Eastwood ◽  
Emma Kneuss ◽  
...  

The PIWI-interacting RNA (piRNA) pathway is a small RNA-based immune system that controls the expression of transposons and maintains genome integrity in animal gonads. In Drosophila, piRNA-guided silencing is achieved, in part, via co-transcriptional repression of transposons by Piwi. This depends on Panoramix (Panx); however, precisely how an RNA binding event silences transcription remains to be determined. Here we show that Nuclear Export Factor 2 (Nxf2) and its co-factor, Nxt1, form a complex with Panx and are required for co-transcriptional silencing of transposons in somatic and germline cells of the ovary. Tethering of Nxf2 or Nxt1 to RNA results in silencing of target loci and the concomitant accumulation of repressive chromatin marks. Nxf2 and Panx proteins are mutually required for proper localization and stability. We mapped the protein domains crucial for the Nxf2/Panx complex formation and show that the amino-terminal portion of Panx is sufficient to induce transcriptional silencing.


Catalysts ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 18
Author(s):  
Yohei Cho ◽  
Akira Yamaguchi ◽  
Masahiro Miyauchi

Methane reforming is an important potential technology for solving both environmental and energy problems. This technology is important because methane is counted as a greenhouse gas, but on the other hand, it can be reformed into industrially valuable compounds. More research has focused on photocatalytic methane reforming, which has a higher activity than thermal catalysts under dark conditions. The reaction selectivity toward specific products in photocatalytic methane reforming is sometimes different from thermal catalyst systems. Herein, we discuss recent advances in photocatalytic methane reforming to provide various strategies for reforming.


2019 ◽  
Author(s):  
Martin H. Fabry ◽  
Filippo Ciabrelli ◽  
Marzia Munafò ◽  
Evelyn L. Eastwood ◽  
Emma Kneuss ◽  
...  

SummaryThe PIWI-interacting RNA (piRNA) pathway is a small RNA-based immune system that controls the expression of transposons and maintains genome integrity in animal gonads. In Drosophila, piRNA-guided silencing is achieved, in part, via co-transcriptional repression of transposons by Piwi. This depends on Panoramix (Panx); however, precisely how an RNA binding event silences transcription remains to be determined. Here we show that Nuclear Export Factor 2 (Nxf2) and its cofactor, Nxt1, form a complex with Panx and are required for co-transcriptional silencing of transposons in somatic and germline cells of the ovary. Tethering of Nxf2 or Nxt1 to RNA results in silencing of target loci and the concomitant accumulation of repressive chromatin marks. Nxf2 and Panx proteins are mutually required for proper localization and stability. We mapped the protein domains crucial for the Nxf2/Panx complex formation and show that the amino-terminal portion of Panx is sufficient to induce transcriptional silencing.


2019 ◽  
Author(s):  
Kensaku Murano ◽  
Yuka W. Iwasaki ◽  
Hirotsugu Ishizu ◽  
Akane Mashiko ◽  
Aoi Shibuya ◽  
...  

SummaryThe PIWI-interacting RNA (piRNA) pathway preserves genomic integrity by repressing transposable elements (TEs) in animal germ cells. Among PIWI-clade proteins in Drosophila, Piwi transcriptionally silences its targets through interactions with cofactors, including Panoramix (Panx) and forms heterochromatin characterized by H3K9me3 and H1. Here, we identified Nxf2, a nuclear RNA export factor (NXF) variant, as a protein that forms complexes with Piwi, Panx, and p15. Panx-Nxf2-p15 complex formation is necessary in the silencing by stabilizing protein levels of Nxf2 and Panx. Notably, ectopic targeting of Nxf2 initiates co-transcriptional repression of the target reporter in a manner independent of H3K9me3 marks or H1. However, continuous silencing requires HP1a and H1. In addition, Nxf2 directly interacts with target TE transcripts in a Piwi-dependent manner. These findings suggest a model in which the Nxf2-Panx-p15 complex enforces the association of Piwi with target transcripts to trigger co-transcriptional repression, prior to heterochromatin formation in the nuclear piRNA pathway.HighlightsNxf2 plays an essential role in the Piwi–piRNA pathwayFormation of Piwi-Panx-Nxf2-p15 (PPNP) complexes stabilizes both Panx and Nxf2The PPNP complex triggers transcriptional silencing before heterochromatin formationNxf2 directly binds to target transcripts in a Piwi-dependent manner


Author(s):  
Raphael Enoque Ferraz de Paiva ◽  
Pedro Paulo Corbi

Gold-based metallodrugs have been used for a wide variety of medical–related applications. Although none of them have reached clinical trials, many compounds show potential for a plethora of possible applications. Platinum compounds, on the other hand, are the leading class of metallodrugs used for the treatment of cancer, with successful representatives worldwide, such as cisplatin, carboplatin and oxaliplatin. In this minireview, we will briefly present the development of metallodrugs based on such metals throughout the year of 2017.


2019 ◽  
Author(s):  
Kang Zhao ◽  
Sha Cheng ◽  
Na Miao ◽  
Ping Xu ◽  
Xiaohua Lu ◽  
...  

AbstractThe repression of transposons by the Piwi-interacting RNA (piRNA) pathway is essential to protect animal germ cells. In Drosophila ovaries, Panoramix (Panx) enforces transcriptional silencing by binding to the target-engaged Piwi-piRNA complex, although the precise mechanisms by which this occurs remain elusive. Here, we show that Panx functions together with a germline specific paralogue of a nuclear export factor, dNxf2, and its cofactor dNxt1 (p15), as a ternary complex to suppress transposon expression. Structural and functional analyses demonstrate that dNxf2 binds Panx via its UBA domain, which plays an important role in transposon silencing. Unexpectedly, dNxf2 interacts directly with dNxf1 (TAP), a general nuclear export factor. As a result, dNxf2 prevents dNxf1 from binding to the FG repeats of the nuclear pore complex, a process required for proper RNA export. Transient tethering of dNxf2 to nascent transcripts leads to their nuclear retention. Therefore, we propose that dNxf2 may function as a Pandas (Panoramix-dNxf2 dependent TAP/p15 silencing) complex, which counteracts the canonical RNA exporting machinery and restricts transposons to the nuclear peripheries. Our findings may have broader implications for understanding how RNA metabolism modulates epigenetic gene silencing and heterochromatin formation.


2017 ◽  
Vol 13 (S336) ◽  
pp. 275-276
Author(s):  
Alejandro Báez-Rubio

AbstractThe detection of hydrogen radio-recombination maser lines (RRLs) toward MWC349A in the year 1989 opened the chance to place constraints on the kinematics of an ionized circumstellar disk around a massive star. Since then, a significant number of observations have allowed improving our understanding of this source to the point that we have established that its ionized wind launching occurs at a distance of ~24 au as claimed by disk wind models. On the other hand, this field of study has undergone considerable development over the last six years with the detection of new RRL maser sources. Here, we present a brief summary of all these recent advances and the promising future prospects.


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