Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Medicinal Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
Philos Trans R Soc Lond B Biol Sci. 2018 Nov 5;373(1762):20180170. doi: 10.1098/rstb.2018.0170.
Metazoan replication-dependent histone mRNAs are the only known cellular mRNAs that are not polyadenylated. Histone mRNAs are present in large amounts only in S-phase cells, and their levels are coordinately regulated with the rate of DNA replication. In mammals, the stemloop at the 3' end of histone mRNA is bound to stemloop binding protein, a protein required for both synthesis and degradation of histone mRNA, and an exonuclease, 3'hExo (ERI1). Histone mRNAs are rapidly degraded when DNA synthesis is inhibited in S-phase cells and at the end of S-phase. Upf1 is also required for rapid degradation of histone mRNA as is the S-phase checkpoint. We report that Smg1 is required for histone mRNA degradation when DNA replication is inhibited, suggesting it is the PI-like kinase that activates Upf1 for histone mRNA degradation. We also show that some mutant Upf1 proteins are recruited to histone mRNAs when DNA replication is inhibited and act as dominant negative factors in histone mRNA degradation. We report that the pathway of rapid histone mRNA degradation when DNA replication is inhibited in S-phase cells that are activating the S-phase checkpoint is similar to the pathway of rapid degradation of histone mRNA at the end of S-phase.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.
后生动物复制依赖性组蛋白 mRNA 是唯一已知的未加 poly(A) 的细胞 mRNA。组蛋白 mRNA 仅在 S 期细胞中大量存在，其水平与 DNA 复制的速度协调调节。在哺乳动物中，组蛋白 mRNA 3' 端的茎环与茎环结合蛋白结合，该蛋白是组蛋白 mRNA 合成和降解所必需的，也是一种外切核酸酶 3'端外切酶（ERI1）。当 S 期细胞中 DNA 合成被抑制和 S 期结束时，组蛋白 mRNA 会迅速降解。Upf1 也需要快速降解组蛋白 mRNA，S 期检查点也是如此。我们报告说，当 DNA 复制被抑制时，Smg1 是组蛋白 mRNA 降解所必需的，这表明它是激活 Upf1 进行组蛋白 mRNA 降解的 PI 样激酶。我们还表明，当 DNA 复制被抑制时，一些突变的 Upf1 蛋白被招募到组蛋白 mRNA 上，并在组蛋白 mRNA 降解中充当显性负因子。我们报告说，当 S 期细胞中的 DNA 复制被抑制并激活 S 期检查点时，快速降解组蛋白 mRNA 的途径与 S 期结束时快速降解组蛋白 mRNA 的途径相似。本文是主题问题“5' 和 3' 修饰控制 RNA 降解”的一部分。
