Recent progress in studying the molecular machines involved in mRNA 3'-end processing

Polyadenylation signals and RNA recognition sites of the 3'-end processing machinery in yeast and human pre-mRNAs.Figure 1 from Kumar et al. (2019) Current Opinion in Structural Biologyl, 59, 143-150.

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.

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.

Abstract

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.

Read the Publication in Current Opinion in Structural Biology (Open Access)

Website Jinek Lab

Website Passmore Lab

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.