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NRDE2 negatively regulates nuclear exosome functions

ABSTRACT: NRDE2 negatively regulates nuclear exosome functions

PROVIDER: PRJNA491937 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7879110_1.fastq.gz	Fastqsanger.gz
	SRR7879110_2.fastq.gz	Fastqsanger.gz
	SRR7879120.fastq.gz	Fastqsanger.gz
	SRR7879120_1.fastq.gz	Fastqsanger.gz
	SRR7879120_2.fastq.gz	Fastqsanger.gz

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NRDE2 negatively regulates nuclear exosome functions

Project description:The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4's key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex (CBC) and ZFC3H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export.

2019-03-14 | GSE120206 | GEO

NRDE2 negatively regulates nuclear exosome functions I

Project description:NRDE2 negatively regulates nuclear exosome functions I

| PRJNA491944 | ENA

NRDE2 negatively regulates nuclear exosome functions IV

Project description:NRDE2 negatively regulates nuclear exosome functions IV

| PRJNA491939 | ENA

NRDE2 negatively regulates nuclear exosome functions II

Project description:NRDE2 negatively regulates nuclear exosome functions II

| PRJNA491941 | ENA

NRDE2 negatively regulates nuclear exosome functions II

Project description:To examine whether NRDE2 can impact the competition between hMTR4 and ALYREF, we performed stranded RNA-seq to detect nuclear RNAs isolated from NRDE2 and control knockdown cells.

2019-03-14 | GSE120203 | GEO

NRDE2 negatively regulates nuclear exosome functions I

Project description:To examine whether NRDE2 can impact the competition between hMTR4 and ALYREF, we performed stranded RNA-seq to detect total RNAs isolated from NRDE2 and control knockdown cells.

2019-03-14 | GSE120202 | GEO

NRDE2 negatively regulates nuclear exosome functions IV

Project description:To examine whether NRDE2 can impact the competition between hMTR4 and ALYREF, we performed stranded RNA-seq to detect RNAs isolated from MTR4 IP in NRDE2 and control knockdown cells.

2019-03-14 | GSE120205 | GEO

NRDE2 acts as a negative regulator of the exosome complex by disrupting hMTR4 interactome

Project description:The RNA exosome complex is the most versatile RNA-degradation machine in eukaryotes that requires MTR4 for every aspect of its nuclear functions. To date, how exosome functions are negatively regulated remains largely unknown. Here, we report the identification of NRDE2 as an inhibitory regulator of exosome functions. NRDE2 tightly and directly interacts with human MTR4 (hMTR4) via its N-terminal domain, resulting in their mutual stabilization. Overexpression of NRDE2 attenuates associations of hMTR4 with the exosome, CBC, TRAMP and NEXT components, resulting in accumulation of exosome target RNAs as well as 3’ extended 5.8S rRNAs. Conversely, in NRDE2 knockdown cells, the association of hMTR4 with CBC, TRAMP or NEXT components are significantly enhanced, accompanied by promoted RNA degradation. Together, our work uncovers NRDE2 as a direct negative regulator of exosome functions that prevents hMTR4 from associating with its interacting partners.

2024-12-31 | GSE79582 | GEO