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Structure and regulation of the nuclear exosome targeting complex guides RNA substrates to the exosome.
<div class='caption-title'>Composite model of the NEXT homodimer structured core</div>
<div class='caption-title'>Interactions at the ZCCHC8 dimerization and MTR4-binding interfaces</div>
Gerlach P, Garland W, Lingaraju M, Salerno-Kochan A, Bonneau F, Basquin J, Jensen TH, Conti E
OpenAccess logo Mol Cell 82 2505-2518.e7 (2022)
Related entries: 7z4z, 7z52

Cited: 5 times
EuropePMC logo PMID: 35688157

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.

Articles - 7z4y mentioned but not cited (1)

  1. Structure and regulation of the nuclear exosome targeting complex guides RNA substrates to the exosome. Gerlach P, Garland W, Lingaraju M, Salerno-Kochan A, Bonneau F, Basquin J, Jensen TH, Conti E. Mol Cell 82 2505-2518.e7 (2022)


Reviews citing this publication (2)

  1. Genetics of human telomere biology disorders. Revy P, Kannengiesser C, Bertuch AA. Nat Rev Genet 24 86-108 (2023)
  2. The making and breaking of tRNAs by ribonucleases. Elder JJH, Papadopoulos R, Hayne CK, Stanley RE. Trends Genet 40 511-525 (2024)

Articles citing this publication (2)

  1. C-terminal determinants for RNA binding motif 7 protein stability and RNA recognition. Sobeh AM, Eichhorn CD. Biophys Chem 292 106928 (2023)
  2. Dual agonistic and antagonistic roles of ZC3H18 provide for co-activation of distinct nuclear RNA decay pathways. Polák P, Garland W, Rathore O, Schmid M, Salerno-Kochan A, Jakobsen L, Gockert M, Gerlach P, Silla T, Andersen JS, Conti E, Jensen TH. Cell Rep 42 113325 (2023)


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