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Structural basis for RNA surveillance by the human nuclear exosome targeting (NEXT) complex
M Rhyan Puno1, Christopher D Lima2
1Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Cell
|June 10, 2022
Summary
Researchers uncovered how the nuclear exosome targeting (NEXT) complex captures RNA for degradation. Cryo-EM structures reveal ZCCHC8, MTR4, and RBM7 collaborate to bind and prepare RNA for the exosome.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- RNA quality control is essential for cellular function.
- The 3' to 5' exosome degrades RNA substrates.
- Co-factors like the NEXT complex are crucial for RNA processing.
Purpose of the Study:
- To elucidate the structural mechanisms of RNA recognition and capture by the NEXT complex.
- To understand the initial steps of RNA handover to the nuclear exosome.
Main Methods:
- Cryogenic electron microscopy (cryo-EM) of human NEXT complexes bound to RNA.
- Structural analysis to determine atomic interactions and complex assembly.
Main Results:
- Cryo-EM structures revealed the architecture of the NEXT complex.
- ZCCHC8 acts as a scaffold, facilitating MTR4 helicase and RBM7 binding.
- Collaborative RNA binding by ZCCHC8, MTR4, and RBM7 facilitates substrate capture and translocation.
- ZCCHC8 regulates MTR4 interactions with the RNA exosome core.
Conclusions:
- The NEXT complex employs a multi-subunit mechanism for RNA surveillance and capture.
- Structural insights explain how the NEXT complex coordinates RNA translocation and delivery to the exosome for degradation.
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