2. Academic Validation
  3. Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease

Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease

  • Elife. 2018 Dec 3;7:e39865. doi: 10.7554/eLife.39865.
Ilaria Pettinati 1,  Pawel Grzechnik 2,  Claudia Ribeiro de Almeida 3,  Jurgen Brem 1,  Michael A McDonough 1,  Somdutta Dhir 3,  Nick J Proudfoot 3,  Christopher J Schofield 1
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Oxford, Oxford, United Kingdom.
  • 2 School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
  • 3 Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
PMID: 30507380 DOI: 10.7554/eLife.39865
Abstract

Replication-dependent (RD) core histone mRNA produced during S-phase is the only known metazoan protein-coding mRNA presenting a 3' stem-loop instead of the otherwise universal polyA tail. A metallo β-lactamase (MBL) fold Enzyme, cleavage and polyadenylation specificity factor 73 (CPSF73), is proposed to be the sole endonuclease responsible for 3' end processing of both mRNA classes. We report cellular, genetic, biochemical, substrate selectivity, and crystallographic studies providing evidence that an additional endoribonuclease, MBL domain containing protein 1 (MBLAC1), is selective for 3' processing of RD histone pre-mRNA during the S-phase of the cell cycle. Depletion of MBLAC1 in cells significantly affects cell cycle progression thus identifying MBLAC1 as a new type of S-phase-specific Cancer target.

Keywords

MBL domain containing protein 1; S-phase; cell biology; chromosomes; endoribonuclease; gene expression; histone pre-mRNA 3' end processing; human; metallo β-lactamase.

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