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Structure and regulation of the nuclear exosome targeting complex guides RNA substrates to the exosome.
- Source :
-
Molecular cell [Mol Cell] 2022 Jul 07; Vol. 82 (13), pp. 2505-2518.e7. Date of Electronic Publication: 2022 Jun 09. - Publication Year :
- 2022
-
Abstract
- In mammalian cells, spurious transcription results in a vast repertoire of unproductive non-coding RNAs, whose deleterious accumulation is prevented by rapid decay. The nuclear exosome targeting (NEXT) complex plays a central role in directing non-functional transcripts to exosome-mediated degradation, but the structural and molecular mechanisms remain enigmatic. Here, we elucidated the architecture of the human NEXT complex, showing that it exists as a dimer of MTR4-ZCCHC8-RBM7 heterotrimers. Dimerization preconfigures the major MTR4-binding region of ZCCHC8 and arranges the two MTR4 helicases opposite to each other, with each protomer able to function on many types of RNAs. In the inactive state of the complex, the 3' end of an RNA substrate is enclosed in the MTR4 helicase channel by a ZCCHC8 C-terminal gatekeeping domain. The architecture of a NEXT-exosome assembly points to the molecular and regulatory mechanisms with which the NEXT complex guides RNA substrates to the exosome.<br />Competing Interests: Declaration of interests E.C. is a member of the Molecular Cell advisory board.<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Nucleus genetics
Cell Nucleus metabolism
DEAD-box RNA Helicases metabolism
DNA Helicases metabolism
Exosome Multienzyme Ribonuclease Complex metabolism
Humans
Protein Binding
RNA Helicases metabolism
RNA Stability genetics
Exosomes genetics
Exosomes metabolism
RNA genetics
RNA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 82
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 35688157
- Full Text :
- https://doi.org/10.1016/j.molcel.2022.04.011