Köhn Marcel, Hüttelmaier Stefan
a Institute of Molecular Medicine, Section for Molecular Cell Biology, Faculty of Medicine, Martin-Luther-University Halle Wittenberg, ZAMED , Halle , Germany.
RNA Biol. 2016;13(4):367-72. doi: 10.1080/15476286.2016.1152439. Epub 2016 Feb 24.
In metazoan the 3'-end processing of histone mRNAs is a conserved process involving the concerted action of many protein factors and the non-coding U7 snRNA. Recently, we identified that the processing of histone pre-mRNAs is promoted by an additional ncRNA, the Y3-derived Y3** RNA. U7 modulates the association of the U7 snRNP whereas Y3** promotes recruitment of CPSF (cleavage and polyadenylation specific factor) proteins to nascent histone transcripts at histone locus bodies (HLBs) in mammals. This enhances the 3'-end cleavage of nascent histone pre-mRNAs and modulates HLB assembly. Here we discuss new insights in the role of ncRNAs in the spatiotemporal control of histone synthesis. We propose that ncRNAs scaffold the formation of functional protein-RNA complexes and their sequential deposition on nascent histone pre-mRNAs at HLBs. These findings add to the multiple roles of ncRNAs in controlling gene expression and may provide new avenues for targeting histone synthesis in cancer.
在多细胞动物中，组蛋白mRNA的3'端加工是一个保守过程，涉及许多蛋白质因子和非编码U7 snRNA的协同作用。最近，我们发现组蛋白前体mRNA的加工由另一种非编码RNA（Y3衍生的Y3** RNA）促进。U7调节U7 snRNP的结合，而Y3**促进哺乳动物组蛋白基因座体（HLB）处CPSF（切割和聚腺苷酸化特异性因子）蛋白募集到新生组蛋白转录本上。这增强了新生组蛋白前体mRNA的3'端切割并调节HLB组装。在这里，我们讨论非编码RNA在组蛋白合成的时空控制中作用的新见解。我们提出，非编码RNA支架功能性蛋白质-RNA复合物的形成及其在HLB处新生组蛋白前体mRNA上的顺序沉积。这些发现增加了非编码RNA在控制基因表达中的多种作用，并可能为靶向癌症中的组蛋白合成提供新途径。
