Department of Biochemistry, RNA Group, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
Nucleic Acids Res. 2012 Nov 1;40(20):10240-53. doi: 10.1093/nar/gks838. Epub 2012 Sep 10.
THO is a multi-protein complex that promotes coupling between transcription and mRNA processing. In contrast to its role in mRNA biogenesis, we show here that the fission yeast THO complex negatively controls the expression of non-coding small nucleolar (sno) RNAs. Accordingly, the deletion of genes encoding subunits of the evolutionarily conserved THO complex results in increased levels of mature snoRNAs. We also show physical and functional connections between THO and components of the TRAMP polyadenylation complex, whose loss of function also results in snoRNA accumulation. Consistent with a role in snoRNA expression, we demonstrate that THO and TRAMP complexes are recruited to snoRNA genes, and that a functional THO complex is required to maintain TRAMP occupancy at sites of snoRNA transcription. Our findings suggest that THO promotes exosome-mediated degradation of snoRNA precursors by ensuring the presence of the TRAMP complex at snoRNA genes. This study unveils an unexpected role for THO in the control of snoRNA expression and provides a new link between transcription and nuclear RNA decay.
THO 是一个促进转录和 mRNA 加工之间偶联的多蛋白复合物。与它在 mRNA 生物发生中的作用相反,我们在这里表明,裂殖酵母 THO 复合物负调控非编码小核仁 (sno) RNA 的表达。因此,编码进化上保守的 THO 复合物亚基的基因缺失导致成熟 snoRNA 水平增加。我们还显示了 THO 与 TRAMP 多聚腺苷酸化复合物成分之间的物理和功能连接,其功能丧失也导致 snoRNA 积累。与 snoRNA 表达的作用一致,我们证明 THO 和 TRAMP 复合物被招募到 snoRNA 基因上,并且功能性 THO 复合物是维持 snoRNA 转录位点 TRAMP 占据所必需的。我们的研究结果表明,THO 通过确保 TRAMP 复合物存在于 snoRNA 基因上来促进外切体介导的 snoRNA 前体降解。这项研究揭示了 THO 在 snoRNA 表达调控中的一个意外作用,并为转录和核 RNA 降解之间提供了一个新的联系。