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NRDE2 negatively regulates nuclear exosome functions I

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE120202 | GEO | 2019/03/14

REPOSITORIES: GEO

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NRDE2 negatively regulates nuclear exosome functions II

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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.

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hMTR4 plays a central role in creating balanced nuclear RNA pools for degradation and export VI

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hMTR4 plays a central role in creating balanced nuclear RNA pools for degradation and export V

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