Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease
- University of Oxford, United Kingdom
- University of Birmingham, United Kingdom
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.
Data availability
Diffraction data have been deposited in PDB under the accession code 4V0H.ChrRNA-seq data generated during this study can be accessed at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=kncnwiswrpapngj&acc=GSE94686
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Human metallo beta lactamase domain containing protein 1 (hMBLAC1)Protein Data Bank, 4V0H.
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Biosynthesis of histone messenger RNA employs a specific 3' end endonucleaseGene Expression Omnibus, GSE94686.
Article and author information
Author details
Christopher J Schofield
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.
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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Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease
eLife 7:e39865.
https://doi.org/10.7554/eLife.39865
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