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

eLife

Ilaria Pettinati¹  Jurgen Brem¹  Christopher J Schofield¹  Michael A McDonough¹  Pawel Grzechnik²  Somdutta Dhir³  Claudia Ribeiro de Almeida³  Nick J Proudfoot³ 

[1] Department of Chemistry, University of Oxford, Oxford, United Kingdom;School of Biosciences, University of Birmingham, Birmingham, United Kingdom;Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom;

关键词: histone pre-mRNA 3' end processing;    MBL domain containing protein 1;    S-phase;    endoribonuclease;    metallo β-lactamase;   

DOI  :  10.7554/eLife.39865

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown