Human NEXT dimer - focused reconstruction of the single MTR4Human NEXT dimer - focused reconstruction of the single MTR4

Structural highlights

7z52 is a 3 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.4Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MTREX_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 PubMed

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.

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 Also

References

  1. Schilders G, van Dijk E, Pruijn GJ. C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing. Nucleic Acids Res. 2007;35(8):2564-72. Epub 2007 Apr 4. PMID:17412707 doi:http://dx.doi.org/10.1093/nar/gkm082
  2. Meola N, Domanski M, Karadoulama E, Chen Y, Gentil C, Pultz D, Vitting-Seerup K, Lykke-Andersen S, Andersen JS, Sandelin A, Jensen TH. Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts. Mol Cell. 2016 Nov 3;64(3):520-533. doi: 10.1016/j.molcel.2016.09.025. Epub 2016 , Oct 27. PMID:27871484 doi:http://dx.doi.org/10.1016/j.molcel.2016.09.025
  3. Gerlach P, Garland W, Lingaraju M, Salerno-Kochan A, Bonneau F, Basquin J, Jensen TH, Conti E. Structure and regulation of the nuclear exosome targeting complex guides RNA substrates to the exosome. Mol Cell. 2022 Jul 7;82(13):2505-2518.e7. PMID:35688157 doi:10.1016/j.molcel.2022.04.011

7z52, resolution 3.40Å

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