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TitlemRNA recognition and packaging by the human transcription-export complex.
Journal, issue, pagesNature, Vol. 616, Issue 7958, Page 828-835, Year 2023
Publish dateApr 5, 2023
AuthorsBelén Pacheco-Fiallos / Matthias K Vorländer / Daria Riabov-Bassat / Laura Fin / Francis J O'Reilly / Farja I Ayala / Ulla Schellhaas / Juri Rappsilber / Clemens Plaschka /
PubMed AbstractNewly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription-export complex (TREX) for nuclear export. However, the ...Newly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription-export complex (TREX) for nuclear export. However, the mechanisms of mRNP recognition and three-dimensional mRNP organization are poorly understood. Here we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the 2-MDa TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon junction complexes. Exon junction complexes can multimerize through ALYREF, which suggests a mechanism for mRNP organization. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact and protect mRNAs to promote their packaging for nuclear export. The organization of mRNP globules provides a framework to understand how mRNP architecture facilitates mRNA biogenesis and export.
External linksNature / PubMed:37020021 / PubMed Central
MethodsEM (single particle) / EM (tomography)
Resolution2.4 - 7.5 Å
Structure data

EMDB-14803, PDB-7znj:
Structure of an ALYREF-exon junction complex hexamer
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-14804: Structure of an endogenous human TREX complex bound to mRNA, composite map
PDB-7znk: Structure of an endogenous human TREX complex bound to mRNA
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-14805: Structure of an endogenous human TREX complex bound to mRNA, map A
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-14806: Structure of an endogenous human TREX complex bound to mRNA, map B
Method: EM (single particle) / Resolution: 5.5 Å

EMDB-14807: Structure of an endogenous human TREX complex bound to mRNA, map C
Method: EM (single particle) / Resolution: 7.5 Å

EMDB-14808: Structure of the human TREX core THO-UAP56 complex (map D)
PDB-7znl: Structure of the human TREX core THO-UAP56 complex
Method: EM (single particle) / Resolution: 3.45 Å

EMDB-14809: Structure of the human TREX core THO-UAP56 complex (map E)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-16633: Structure of an ALYREF-exon junction complex hexamer, obtained from TREX-EJC-RNA sample
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-16753: Tomogram of purified human TREX-mRNPs
Method: EM (tomography)

EMDB-17215: Composite map of the human TREX core THO-UAP56 complex
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
  • human (human)
KeywordsGENE REGULATION / transcription-exort complex / TREX / splicing / exon junction complex / EJC / RNA export / RNA binding proteins / transcription and export complex / RNA packaging / RNA binding protein / gene expression

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