A Current Opinion in Structural Biology article by the labs of Martin Jinek and Lori Passmore discusses recent advances made in gaining mechanistic insights into mRNA 3'-end processing. The article is part of a themed issue on protein nucleic acid interactions edited by Frédéric Allain and Martin Jinek.
- 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.
Figure, highlights and abstract from Kumar et al. (2019) Current Opinion in Structural Biologyl, 59, 143-150 published under the CC BY 4.0 license.