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A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila [ncRNA-seq]

ABSTRACT: A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila [ncRNA-seq]

PROVIDER: PRJNA464399 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7128406.fastq.gz	Fastqsanger.gz
	SRR7128407.fastq.gz	Fastqsanger.gz

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A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila [ncRNA-seq]

Project description:Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNAs that bind Piwi proteins to silence transposons and to regulate gene expression. In Drosophila germ cells, the Aubergine (Aub)-Argonaute 3 (Ago3)-dependent ping-pong cycle generates most germline piRNAs. Loading of anti-sense piRNAs amplified by this cycle enables Piwi to enter the nucleus and silence transposons. Nuclear localization is crucial for Piwi function in transposon silencing, but how this process is regulated remains unknown. It is also not known whether any of the components of the nuclear pore complex (NPC) directly function in the piRNA pathway. Here, we show that nucleoporin 358 (Nup358) and Piwi interact with each other and that a germline knockdown (GLKD) of Nup358 with short hairpin RNA prevents Piwi entry into the nucleus. The Nup358 GLKD also activated transposons, increased genomic instability, and derailed piRNA biogenesis because of a combination of decreased piRNA precursor transcription and a collapse of the ping-pong cycle. Our results point to a critical role for Nup358 in the piRNA pathway, laying the foundation for future studies to fully elucidate the mechanisms by which Nup358 contributes to piRNA biogenesis and transposon silencing.

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A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila [RNA-Seq]

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A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila

Project description:A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila

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A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila [GRO-seq]

Project description:A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila [GRO-seq]

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A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila.

Project description:Piwi-interacting RNAs (piRNAs) are a class of small noncoding RNAs that bind Piwi proteins to silence transposons and to regulate gene expression. In Drosophila germ cells, the Aubergine (Aub)-Argonaute 3 (Ago3)-dependent ping-pong cycle generates most germline piRNAs. Loading of antisense piRNAs amplified by this cycle enables Piwi to enter the nucleus and silence transposons. Nuclear localization is crucial for Piwi function in transposon silencing, but how this process is regulated remains unknown. It is also not known whether any of the components of the nuclear pore complex (NPC) directly function in the piRNA pathway. Here, we show that nucleoporin 358 (Nup358) and Piwi interact with each other and that a germline knockdown (GLKD) of Nup358 with short hairpin RNA prevents Piwi entry into the nucleus. The Nup358 GLKD also activated transposons, increased genomic instability, and derailed piRNA biogenesis because of a combination of decreased piRNA precursor transcription and a collapse of the ping-pong cycle. Our results point to a critical role for Nup358 in the piRNA pathway, laying the foundation for future studies to fully elucidate the mechanisms by which Nup358 contributes to piRNA biogenesis and transposon silencing.

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Nucleoporin Nup358 drives the differentiation of myeloid-biased multipotent progenitors by modulating HDAC3 nuclear translocation

Project description:We report that Nup358, a nucleoporin linked to acute myeloid leukemia and myeloproliferative neoplasms, is required for the developmental progression of early myeloid progenitors. We found that loss of Nup358 in mice is associated with the accumulation of myeloid-primed multipotent progenitors (MPPs) in bone marrow and the loss of myeloid-committed progenitors and mature myeloid cells. Accumulated MPPs in Nup358 knockout mice are greatly restricted to megakaryocyte/erythrocyte biased MPP2 cells and fail to progress into committed myeloid progenitors.

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Project description:The PIWI-interacting RNA (piRNA) pathway is an important mechanism to suppress transposon activation in the germline that is highly conserved between Drosophila and mammals. This pathway starts from transcribing piRNA clusters to generate long piRNA precursors. The majority of piRNA clusters lacks a conventional promoter, and therefore their transcription is considered to utilize a noncanonical mechanism. However, information regarding transcriptional regulation of piRNA clusters is limited. Here, we report that the fly KAT6 acetyltransferase, Enok, is important for transposon silencing in the germline. Further small RNA-seq analysis revealed that Enok is critical for piRNA production from a specific subset of piRNA clusters including 42AB, one of the two major sources of piRNAs. Enok is the major enzyme for establishing the H3K23ac mark, and was shown to promote gene expression by acetylating H3K23. Surprisingly, our RNA-seq and ChIP-seq/ChIP-qPCR results suggest that Enok regulates expression of genes involved in the piRNA production by H3K23ac-dependent mechanisms, and also promotes transcription at piRNA clusters through H3K23ac-independent pathways. Our co-immunoprecipitation assay further suggests that Enok interacts with RNA polymerase II to facilitate transcription of piRNA clusters. Taken together, our study provides novel insights into the regulation of noncanonical transcription at piRNA clusters and transposon silencing.

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Drosophila melanogaster

Project description:A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila [RNA-Seq]

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A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-05-14 | GSE85715 | GEO