Mullen Thomas E, Marzluff William F
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Genes Dev. 2008 Jan 1;22(1):50-65. doi: 10.1101/gad.1622708.
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'.
组蛋白mRNA在S期结束时或DNA复制受到抑制时会迅速降解。组蛋白mRNA的末端是一个保守的茎环结构，而不是聚腺苷酸尾巴。组蛋白mRNA的降解需要茎环序列，该序列结合茎环结合蛋白（SLBP）、组蛋白mRNA的活跃翻译以及茎环靠近终止密码子的位置。我们报告称，组蛋白mRNA降解的第一步是在DNA复制受到抑制后以及S期结束时，在组蛋白mRNA的3'末端添加尿苷。Lsm1是组蛋白mRNA降解所必需的，并且在DNA复制受到抑制后，存在于组蛋白mRNA 3'末端包含SLBP的复合物中。我们克隆了从其5'端和3'端都已部分降解的降解中间体。RNA干扰实验表明，外切体和5'到3'衰变途径成分都是降解所必需的，然后单个组蛋白mRNA会同时从5'到3'和从3'到5'进行降解。
