Mechanistic insights into mRNA 3′-end processing

https://doi.org/10.1016/j.sbi.2019.08.001Get rights and content
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Highlights

  • Integrated structural biology approaches have provided new insights into the mechanism of eukaryotic mRNA 3′-end processing.

  • The polymerase modules of yeast and human cleavage and polyadenylation factors share a conserved architecture.

  • CryoEM structures of human CPSF have revealed the mechanism of AAUAAA polyadenylation signal recognition.

  • Cleavage and polyadenylation of mRNA 3′-ends likely involves a dynamic assembly of CPF/CPSF and accessory factors.

The polyadenosine (poly(A)) tail found on the 3′-end of almost all eukaryotic mRNAs is important for mRNA stability and regulation of translation. mRNA 3′-end processing occurs co-transcriptionally and involves more than 20 proteins to specifically recognize the polyadenylation site, cleave the pre-mRNA, add a poly(A) tail, and trigger transcription termination. The polyadenylation site (PAS) defines the end of the 3′-untranslated region (3′-UTR) and, therefore, selection of the cleavage site is a critical event in regulating gene expression. Integrated structural biology approaches including biochemical reconstitution of multi-subunit complexes, cross-linking mass spectrometry, and structural analyses by X- ray crystallography and single-particle electron cryo-microscopy (cryoEM) have enabled recent progress in understanding the molecular mechanisms of the mRNA 3′-end processing machinery. Here, we describe new molecular insights into pre-mRNA recognition, cleavage and polyadenylation.

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