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Post-transcriptional Gene Silencing Mediated by microRNAs is Controlled by Nucleoplasmic Sfpq

ABSTRACT: Post-transcriptional Gene Silencing Mediated by microRNAs is Controlled by Nucleoplasmic Sfpq

PROVIDER: PRJNA349976 | ENA |

REPOSITORIES: ENA

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Dataset's files

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			Action	DRS
	SRR4437090_1.fastq.gz	Fastqsanger.gz
	SRR4437090_2.fastq.gz	Fastqsanger.gz
	SRR4437100.fastq.gz	Fastqsanger.gz
	SRR4437110.fastq.gz	Fastqsanger.gz
	SRR4437091_1.fastq.gz	Fastqsanger.gz

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Post-transcriptional Gene Silencing Mediated by microRNAs is Controlled by Nucleoplasmic Sfpq [Agilent]

Project description:There is a growing body of evidence about the presence and the activity of the miRISC in the nucleus of mammalian cells. Here, we show by quantitative proteomic analysis that Ago2 interacts with nucleoplasmic Sfpq in a RNA-dependent fashion. By HITS-CLIP and transcriptomic analyses, we demonstrated that Sfpq directly controls the miRNA targeting of a subset of crucial miRNA-target mRNAs when it binds locally. Sfpq modulates miRNA targeting in both nucleoplasm and cytoplasm, indicating a nucleoplasmic imprinting of Sfpq-target mRNAs that influence miRNA targeting in both cellular compartments. Mechanistically, Sfpq binds to a sizeable set of long 3’UTR forming long aggregates to optimize miRNA position/recruitment to selected binding sites, as we show for Lin28A mRNA. These results extend the miRNA-mediated post-transcriptional gene silencing into the nucleoplasm and indicate that an unique Sfpq-dependent post-transcriptional strategy for controlling both nuclear and cytoplasmic gene expression takes place in cells during physio-pathological events.

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Post-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq.

Project description:There is a growing body of evidence about the presence and the activity of the miRISC in the nucleus of mammalian cells. Here, we show by quantitative proteomic analysis that Ago2 interacts with the nucleoplasmic protein Sfpq in an RNA-dependent fashion. By a combination of HITS-CLIP and transcriptomic analyses, we demonstrate that Sfpq directly controls the miRNA targeting of a subset of binding sites by local binding. Sfpq modulates miRNA targeting in both nucleoplasm and cytoplasm, indicating a nucleoplasmic commitment of Sfpq-target mRNAs that globally influences miRNA modes of action. Mechanistically, Sfpq binds to a sizeable set of long 3'UTRs forming aggregates to optimize miRNA positioning/recruitment at selected binding sites, including let-7a binding to Lin28A 3'UTR. Our results extend the miRNA-mediated post-transcriptional gene silencing into the nucleoplasm and indicate that an Sfpq-dependent strategy for controlling miRNA activity takes place in cells, contributing to the complexity of miRNA-dependent gene expression control.

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Post-transcriptional Gene Silencing Mediated by microRNAs is Controlled by Nucleoplasmic Sfpq

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

2017-10-20 | GSE89033 | GEO

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Project description:Post-transcriptional Gene Silencing Mediated by microRNAs is Controlled by Nucleoplasmic Sfpq [Agilent]

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Microarray of zebrafish (Danio rerio) sfpq-/-;Tg(mnx1:GFP) against sfpq+/+;Tg(mnx1:GFP) and sfpq+/-;Tg(mnx1:GFP) siblings at 24 hpf

Project description:Phenotypic characterisation of our zebrafish sfpq homozygous mutants revealed a restricted set of specific defects, unexpected for a protein expressed ubiquitously and involved in such general mechanisms. The CNS was prominently affected, showing brain boundary and axonal defects associated with absence of motility. To investigate a possible specificity in SFPQ functional targets by microarray RNA profiling analysis, comparing the transcriptome of the sfpq homozygous mutants with its wild type and heterozygous siblings at the earliest stage at which the phenotype is robustly recognizable.

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Project description:Post-transcriptional Gene Silencing Mediated by microRNAs is Controlled by Nucleoplasmic Sfpq [RIP-Seq]

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Project description:Post-transcriptional Gene Silencing Mediated by microRNAs is Controlled by Nucleoplasmic Sfpq [HITS-CLIP]

| PRJNA349980 | ENA