Spt6 association with RNAPII directs mRNA turnover during transcription

Spt6 is an essential histone chaperone that mediates nucleosome reassembly during gene transcription. Spt6 interacts with elongating RNA polymerase II (RNAPII) via a tandem Src2 homology (tSH2) domain, but it is not known whether this particular interaction is required for the nucleosome reassembly activity of Spt6. Here, we show that Spt6 recruitment to genes and its nucleosome reassembly functions are largely independent of association with RNAPII. Instead, the Spt6-RNAPII association is required for post-transcriptional mRNA turnover. Mechanistically, association of Spt6 with RNAPII couples the Ccr4-Not complex to the transcribed regions of genes, which we show regulates the timely deadenylation and degradation of a broad range of mRNAs including those required for cell cycle progression. Thus, our findings reveal an unexpected control mechanism for mRNA turnover facilitated by a histone chaperone during transcription.Spt6是一类关键的组蛋白伴侣（histone chaperone），可介导基因转录过程中的核小体重组装。Spt6通过串联Src2同源（tSH2）结构域与延伸中的RNA聚合酶II（RNAPII）发生相互作用，但目前尚不明确该特定相互作用是否为Spt6的核小体重组装活性所必需。本研究证实，Spt6被招募至基因区域的过程及其核小体重组装功能，在很大程度上不依赖于与RNAPII的结合。与之相反，Spt6与RNAPII的相互结合是转录后mRNA周转过程所必需的。从机制层面而言，Spt6与RNAPII的结合可将Ccr4-Not复合物招募至基因的转录区域，我们证实该过程可调控包括细胞周期进程相关mRNA在内的多种mRNA的及时脱腺苷酸化与降解。综上，本研究揭示了组蛋白伴侣在转录过程中介导mRNA周转的一种此前未被发现的调控机制。