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.
journal_name
Elifejournal_title
eLifeauthors
Pettinati I,Grzechnik P,Ribeiro de Almeida C,Brem J,McDonough MA,Dhir S,Proudfoot NJ,Schofield CJdoi
10.7554/eLife.39865subject
Has Abstractpub_date
2018-12-03 00:00:00issn
2050-084Xpii
39865journal_volume
7pub_type
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