scholarly journals Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing

2019 ◽  
Author(s):  
Kensaku Murano ◽  
Yuka W. Iwasaki ◽  
Hirotsugu Ishizu ◽  
Akane Mashiko ◽  
Aoi Shibuya ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Transcriptional Silencing ◽  
List Type ◽  
Dependent Manner ◽  
Heterochromatin Formation ◽  
Protein Levels ◽  
Nuclear Rna ◽  
Rna Export ◽  
Nuclear Rna Export ◽  
Pirna Pathway

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

scholarly journals Nuclear RNA export factor variant initiates piRNA‐guided co‐transcriptional silencing

2019 ◽  
Vol 38 (17) ◽  
Author(s):  
Kensaku Murano ◽  
Yuka W Iwasaki ◽  
Hirotsugu Ishizu ◽  
Akane Mashiko ◽  
Aoi Shibuya ◽  
...  
Keyword(s):  
Transcriptional Silencing ◽  
Nuclear Rna ◽  
Rna Export ◽  
Nuclear Rna Export

scholarly journals Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K

2000 ◽  
Vol 74 (20) ◽  
pp. 9353-9361 ◽  
Author(s):  
Hal P. Bogerd ◽  
Heather L. Wiegand ◽  
Jin Yang ◽  
Bryan R. Cullen
Keyword(s):  
Nuclear Export ◽  
Biological Activities ◽  
Endogenous Retrovirus ◽  
Viral Rna ◽  
Human Endogenous Retrovirus ◽  
Nuclear Rna ◽  
Rna Export ◽  
Nuclear Rna Export ◽  
Hiv 1 ◽  
Rev Protein

ABSTRACT Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular Crm1 export factor. Human endogenous retrovirus K, a family of ancient endogenous retroviruses that is not related to the exogenous retrovirus HIV-1, was recently shown to also encode a Crm1-dependent nuclear RNA export factor, termed K-Rev. Although HIV-1 Rev and K-Rev display little sequence identity, they share the ability not only to bind to Crm1 and to RNA but also to form homomultimers and shuttle between nucleus and cytoplasm. We have used mutational analysis to identify sequences in the 105-amino-acid K-Rev protein required for each of these distinct biological activities. While mutations in K-Rev that inactivate any one of these properties also blocked K-Rev-dependent nuclear RNA export, several K-Rev mutants were comparable to wild type when assayed for any of these individual activities yet nevertheless defective for RNA export. Although several nonfunctional K-Rev mutants acted as dominant negative inhibitors of K-Rev-, but not HIV-1 Rev-, dependent RNA export, these were not defined by their inability to bind to Crm1, as is seen with HIV-1 Rev. In total, this analysis suggests a functional architecture for K-Rev that is similar to, but distinct from, that described for HIV-1 Rev and raises the possibility that viral RNA export mediated by the ∼25 million-year-old K-Rev protein may require an additional cellular cofactor that is not required for HIV-1 Rev function.

scholarly journals The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation

2019 ◽  
Author(s):  
Julia Batki ◽  
Jakob Schnabl ◽  
Juncheng Wang ◽  
Dominik Handler ◽  
Veselin I. Andreev ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Rna Binding ◽  
Transcriptional Silencing ◽  
Genome Integrity ◽  
Rna Transport ◽  
Heterochromatin Formation ◽  
Genome Defense ◽  
Molecular Events ◽  
Pirna Pathway ◽  
Transport Receptor

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.

scholarly journals 68P Deciphering the interplay between nuclear RNA export factors and long non-coding RNAs in breast cancer metabolism

2020 ◽  
Vol 31 ◽  
pp. S38
Author(s):  
C. Klec ◽  
D. Schwarzenbacher ◽  
B. Gottschalk ◽  
R. Margit ◽  
F. Prinz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metabolism ◽  
Nuclear Rna ◽  
Rna Export ◽  
Non Coding Rnas ◽  
Nuclear Rna Export ◽  
Rna Export Factors

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

2021 ◽  
Author(s):  
Sheng Wang ◽  
Xiaohua Lu ◽  
Ding Qiu ◽  
Yang Yu
Keyword(s):  
Transcriptional Repression ◽  
Nuclear Export ◽  
The Other ◽  
Genetic Conflict ◽  
Heterochromatin Formation ◽  
Argonaute Proteins ◽  
Recent Advances ◽  
Other Hand ◽  
Pirna Pathway

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.

scholarly journals Ser7 of RNAPII-CTD facilitates heterochromatin formation by linking ncRNA to RNAi

2017 ◽  
Vol 114 (52) ◽  
pp. E11208-E11217 ◽  
Author(s):  
Takuya Kajitani ◽  
Hiroaki Kato ◽  
Yuji Chikashige ◽  
Chihiro Tsutsumi ◽  
Yasushi Hiraoka ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Chromatin Structure ◽  
Molecular Basis ◽  
Rna Binding ◽  
Noncoding Rnas ◽  
Transcriptional Silencing ◽  
Binding Activity ◽  
Dependent Manner ◽  
Heterochromatin Formation ◽  
A Subunit

Some long noncoding RNAs (ncRNAs) transcribed by RNA polymerase II (RNAPII) are retained on chromatin, where they regulate RNAi and chromatin structure. The molecular basis of this retention remains unknown. We show that in fission yeast serine 7 (Ser7) of the C-terminal domain (CTD) of RNAPII is required for efficient siRNA generation for RNAi-dependent heterochromatin formation. Surprisingly, Ser7 facilitates chromatin retention of nascent heterochromatic RNAs (hRNAs). Chromatin retention of hRNAs and siRNA generation requires both Ser7 and an RNA-binding activity of the chromodomain of Chp1, a subunit of the RNA-induced transcriptional silencing (RITS) complex. Furthermore, RITS associates with RNAPII in a Ser7-dependent manner. We propose that Ser7 promotes cotranscriptional chromatin retention of hRNA by recruiting the RNA-chromatin connector protein Chp1, which facilitates RNAi-dependent heterochromatin formation. Our findings reveal a function of the CTD code: linking ncRNA transcription to RNAi for heterochromatin formation.

scholarly journals Nuclear RNA export

2003 ◽  
Vol 116 (4) ◽  
pp. 587-597 ◽  
Author(s):  
B. R. Cullen
Keyword(s):  
Nuclear Rna ◽  
Rna Export ◽  
Nuclear Rna Export
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