Molecular Insights into mRNA Polyadenylation and Deadenylation

Int J Mol Sci. 2022 Sep 20;23(19):10985. doi: 10.3390/ijms231910985.

Abstract

Poly(A) tails are present on almost all eukaryotic mRNAs, and play critical roles in mRNA stability, nuclear export, and translation efficiency. The biosynthesis and shortening of a poly(A) tail are regulated by large multiprotein complexes. However, the molecular mechanisms of these protein machineries still remain unclear. Recent studies regarding the structural and biochemical characteristics of those protein complexes have shed light on the potential mechanisms of polyadenylation and deadenylation. This review summarizes the recent structural studies on pre-mRNA 3'-end processing complexes that initiate the polyadenylation and discusses the similarities and differences between yeast and human machineries. Specifically, we highlight recent biochemical efforts in the reconstitution of the active human canonical pre-mRNA 3'-end processing systems, as well as the roles of RBBP6/Mpe1 in activating the entire machinery. We also describe how poly(A) tails are removed by the PAN2-PAN3 and CCR4-NOT deadenylation complexes and discuss the emerging role of the cytoplasmic poly(A)-binding protein (PABPC) in promoting deadenylation. Together, these recent discoveries show that the dynamic features of these machineries play important roles in regulating polyadenylation and deadenylation.

Keywords: 3′-end processing; CCR4-NOT; PABPC; PAN2-PAN3; RBBP6/Mpe1; RNA-binding protein; deadenylation; poly(A) tail; polyadenylation.

Publication types

  • Review

MeSH terms

  • DNA-Binding Proteins / metabolism
  • Exoribonucleases / genetics
  • Humans
  • Multiprotein Complexes / metabolism
  • Poly(A)-Binding Proteins / metabolism
  • Polyadenylation*
  • RNA Precursors / metabolism
  • RNA Stability
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Mpe1 protein, S cerevisiae
  • Multiprotein Complexes
  • Poly(A)-Binding Proteins
  • RNA Precursors
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • RBBP6 protein, human
  • Ubiquitin-Protein Ligases
  • Exoribonucleases