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组蛋白信使 RNA 的生物合成需要一种特异的 3' 端内切核酸酶。

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

机构信息

Department of Chemistry, University of Oxford, Oxford, United Kingdom.

School of Biosciences, University of Birmingham, Birmingham, United Kingdom.

出版信息

Elife. 2018 Dec 3;7:e39865. doi: 10.7554/eLife.39865.

DOI:10.7554/eLife.39865
PMID:30507380
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6303110/
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.

摘要

复制依赖性 (RD) 核心组蛋白 mRNA 是在 S 期产生的，它是唯一已知的后生动物蛋白编码 mRNA，具有 3'茎环结构，而不是通常的多聚 A 尾。一种金属β-内酰胺酶 (MBL) 折叠酶，切割和多聚腺苷酸化特异性因子 73 (CPSF73)，被提议是唯一负责两种 mRNA 类别的 3'末端加工的内切核酸酶。我们报告了细胞、遗传、生化、底物选择性和晶体学研究，提供了证据表明，另一种内切核糖核酸酶，MBL 结构域包含蛋白 1 (MBLAC1)，在细胞周期的 S 期时，对 RD 组蛋白前体 mRNA 的 3'加工具有选择性。在细胞中耗尽 MBLAC1 会显著影响细胞周期进程，从而将 MBLAC1 鉴定为一种新型的 S 期特异性癌症靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/ffc3c66099fa/elife-39865-resp-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/ffc3c66099fa/elife-39865-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/b707cf04fa4b/elife-39865-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/85e14c8dc487/elife-39865-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/1a5b1cf0da31/elife-39865-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/b06c9042cf19/elife-39865-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/029c0fee14d0/elife-39865-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/189647def07f/elife-39865-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/b31130783ca2/elife-39865-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/59d2c09b9cb4/elife-39865-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/19019214567c/elife-39865-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/16453ef25cb0/elife-39865-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/9e829751cfb9/elife-39865-fig4-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/8c48a6ef985d/elife-39865-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/9c651ab2aa98/elife-39865-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1101/6303110/ffc3c66099fa/elife-39865-resp-fig1.jpg

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