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

Ilaria Pettinati; Pawel Grzechnik; Claudia Ribeiro de Almeida; Jurgen Brem; Michael A. McDonough; Somdutta Dhir; Nick J. Proudfoot; Christopher J. Schofield

doi:10.7554/eLife.39865

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

Ilaria Pettinati, Pawel Grzechnik, Claudia Ribeiro de Almeida, Jurgen Brem, Michael A. McDonough, Somdutta Dhir, Nick J. Proudfoot, Christopher J. Schofield^*

^*Corresponding author for this work

Division of Molecular & Cellular Function (L5)

Research output: Contribution to journal › Article › peer-review

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 b-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.

Original language	English
Article number	e39865
Journal	eLife
Volume	7
DOIs	https://doi.org/10.7554/eLife.39865
Publication status	Published - 1 Dec 2018

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10.7554/eLife.39865

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title = "Biosynthesis of histone messenger RNA employs a specific 3{\textquoteright} end endonuclease",

abstract = "Replication-dependent (RD) core histone mRNA produced during S-phase is the only known metazoan protein-coding mRNA presenting a 3{\textquoteright} stem-loop instead of the otherwise universal polyA tail. A metallo b-lactamase (MBL) fold enzyme, cleavage and polyadenylation specificity factor 73 (CPSF73), is proposed to be the sole endonuclease responsible for 3{\textquoteright} 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{\textquoteright} 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.",

author = "Ilaria Pettinati and Pawel Grzechnik and {de Almeida}, {Claudia Ribeiro} and Jurgen Brem and McDonough, {Michael A.} and Somdutta Dhir and Proudfoot, {Nick J.} and Schofield, {Christopher J.}",

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year = "2018",

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doi = "10.7554/eLife.39865",

language = "English",

volume = "7",

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AU - Pettinati, Ilaria

AU - Grzechnik, Pawel

AU - de Almeida, Claudia Ribeiro

AU - Brem, Jurgen

AU - McDonough, Michael A.

AU - Dhir, Somdutta

AU - Proudfoot, Nick J.

AU - Schofield, Christopher J.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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 b-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.

AB - 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 b-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.

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DO - 10.7554/eLife.39865

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SN - 2050-084X

VL - 7

JO - eLife

JF - eLife

M1 - e39865

ER -

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

Abstract

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