In eukaryotic cells, the DNA carrying the genetic information is in the nucleus and the ribosomes that translate the genetic information are in the cytoplasm, they are separated by the nuclear membrane. RNA is the important mediation to cross nuclear membrane for genetic information. An RNA quality monitoring system is ubiquitous in the nucleus to rapidly identify and degrade mRNAs carrying erroneous genetic information or abnormalities, thereby ensuring accurate transmission of genetic information.
The highly conserved exosome complex is the most versatile RNA surveillance and degradation machine. Yet how it is negatively regulated remains clearly unknown.
Recently, researchers from China have discovered the first negative regulation factor NRDE2 of the RNA exosome complex. They clarified the functional mechanism how NRDE2 inhibits the RNA exosome complex and provided an important regulation mode of RNA nucleus export and degradation.
NRDE2 forms a 1:1 complex with MTR4(a nuclear exosome cofactor critical for exosome recruitment). The NRDE2 locates in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation to ensures efficient mRNA nuclear export.
The 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. NRDE2 also inhibits the interaction between MTR4 and exosome, providing another important level of negative regulation. This NRDE2-mediated exosome negative regulation is critical for the dry maintenance of mouse embryonic stem cells.
The study first discovered the negative regulation factor NRDE2 of exosome , which explained its molecular mechanism and biological significance of inhibiting RNA degradation and promoting RNA nuclear transport, revealing a key mode regulating the nucleation or degradation of newborn transcripts, and It has opened up new directions for the field of RNA degradation research.
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