7z52
Human NEXT dimer - focused reconstruction of the single MTR4
Structural highlights
FunctionMTREX_HUMAN Component of exosome targeting complexes. Subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that directs a subset of non-coding short-lived RNAs for exosomal degradation. Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (PubMed:27871484). May be involved in pre-mRNA splicing. Associated with the RNA exosome complex and involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA.[1] [2] Publication Abstract from PubMedIn 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. 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. 2022 Jul 7;82(13):2505-2518.e7. doi: 10.1016/j.molcel.2022.04.011. Epub , 2022 Jun 9. PMID:35688157[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
