Department of Cell & Developmental Biology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Department of Cell & Developmental Biology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Mol Cell. 2014 Apr 10;54(1):156-165. doi: 10.1016/j.molcel.2014.03.026.
Antisense transcription is widespread in many genomes; however, how much is functional is hotly debated. We are investigating functionality of a set of long noncoding antisense transcripts, collectively called COOLAIR, produced at Arabidopsis FLOWERING LOCUS C (FLC). COOLAIR initiates just downstream of the major sense transcript poly(A) site and terminates either early or extends into the FLC promoter region. We now show that splicing of COOLAIR is functionally important. This was revealed through analysis of a hypomorphic mutation in the core spliceosome component PRP8. The prp8 mutation perturbs a cotranscriptional feedback mechanism linking COOLAIR processing to FLC gene body histone demethylation and reduced FLC transcription. The importance of COOLAIR splicing in this repression mechanism was confirmed by disrupting COOLAIR production and mutating the COOLAIR proximal splice acceptor site. Our findings suggest that altered splicing of a long noncoding transcript can quantitatively modulate gene expression through cotranscriptional coupling mechanisms.
反义转录在许多基因组中广泛存在；然而，有多少是具有功能的，这是一个激烈争论的问题。我们正在研究一组长非编码反义转录本的功能，这些转录本统称为 COOLAIR，它们在拟南芥开花位点 C (FLC) 产生。COOLAIR 就在主要的有义转录物 poly(A) 位点的下游开始，并在早期终止或延伸到 FLC 启动子区域。我们现在表明，COOLAIR 的剪接具有功能重要性。这是通过分析核心剪接体成分 PRP8 的一个弱等位基因突变来揭示的。prp8 突变扰乱了 COOLAIR 加工与 FLC 基因体组蛋白去甲基化和减少 FLC 转录之间的共转录反馈机制。通过破坏 COOLAIR 的产生和突变 COOLAIR 近端剪接受体位点，证实了 COOLAIR 剪接在这种抑制机制中的重要性。我们的研究结果表明，长非编码转录本的剪接改变可以通过共转录偶联机制定量调节基因表达。
