G & D：寡聚鸟苷化介导的组蛋白mRNA的降解

在1月1日的Genes  &  Development杂志上，Thomas  Mullen和William  Marzluff博士通过研究揭示出了哺乳动物组蛋白mRNA的降解原理。

组蛋白mRNA在S期末会迅速降解，但是这个过程的生物学机制一直含糊不清，因为后生动物的组蛋白mRNAs有一个非常独特的结构：不是典型的3'  poly(A)尾，而是一段保守的3'茎环结构。

Mullen和Marzluff博士的研究成果表明，当一些尿苷添加到组蛋白mRNAs的3'端后，转录产物就会去帽（decapped），并从两端开始降解。参与降解的是普通的mRNA衰变机器（mRNA  decay  machinery）。

此项工作也是首次展示了寡聚尿苷化对哺乳动物mRNA转录产物半衰期的调控。

资料来源：Cold  Spring  Harbor  Laboratory

生物谷推荐原始出处：
GENES & DEVELOPMENT 22:50-65, 2008

Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'

Thomas E. Mullen1 and William F. Marzluff1,2,3

1 Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; 2 Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA

Histone mRNAs are rapidly degraded at the end of S phase or when DNA replication is inhibited. Histone mRNAs end in a conserved stem–loop rather than a poly(A) tail. Degradation of histone mRNAs requires the stem–loop sequence, which binds the stem–loop-binding protein (SLBP), active translation of the histone mRNA, and the location of the stem–loop close to the termination codon. We report that the initial step in histone mRNA degradation is the addition of uridines to the 3' end of the histone mRNA, both after inhibition of DNA replication and at the end of S phase. Lsm1 is required for histone mRNA degradation and is present in a complex containing SLBP on the 3' end of histone mRNA after inhibition of DNA replication. We cloned degradation intermediates that had been partially degraded from both the 5' and the 3' ends. RNAi experiments demonstrate that both the exosome and 5'-to-3' decay pathway components are required for degradation, and individual histone mRNAs are then degraded simultaneously 5' to 3' and 3' to 5'.

[Keywords: Histone; cell cycle; mRNA stability; decapping; exosome; oligouridylation]]

Received October 3, 2007; revised version accepted November 5, 2007.

3 Corresponding author.

E-MAIL marzluff@med.unc.edu ; FAX (919) 962-1274.