1. Cell Biology
  2. Chromosomes and Gene Expression
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Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease

  1. Ilaria Pettinati
  2. Pawel Grzechnik
  3. Claudia Ribeiro de Almeida
  4. Jurgen Brem
  5. Michael A McDonough
  6. Somdutta Dhir
  7. Nick J Proudfoot  Is a corresponding author
  8. Christopher J Schofield  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. University of Birmingham, United Kingdom
Research Article
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Cite this article as: eLife 2018;7:e39865 doi: 10.7554/eLife.39865

Abstract

Replication dependent (RD) core histone mRNA produced during S-phase is the only known 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.

Article and author information

Author details

  1. Ilaria Pettinati

    Department of Chemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  2. Pawel Grzechnik

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  3. Claudia Ribeiro de Almeida

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Jurgen Brem

    Department of Chemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  5. Michael A McDonough

    Department of Chemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  6. Somdutta Dhir

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  7. Nick J Proudfoot

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    For correspondence
    nicholas.proudfoot@path.ox.ac.uk
    Competing interests
    Nick J Proudfoot, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8646-3222
  8. Christopher J Schofield

    Department of Chemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    christopher.schofield@chem.ox.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0290-6565

Funding

Wellcome (107928/Z/15/Z)

  • Nick J Proudfoot

Medical Research Council

  • Christopher J Schofield

Wellcome

  • Christopher J Schofield

Cancer Research UK

  • Christopher J Schofield

Biotechnology and Biological Sciences Research Council

  • Christopher J Schofield

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Torben Heick Jensen, Aarhus University, Denmark

Publication history

  1. Received: July 5, 2018
  2. Accepted: November 30, 2018
  3. Accepted Manuscript published: December 3, 2018 (version 1)

Copyright

© 2018, Pettinati et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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