CRUK Applied Computational Biology and Bioinformatics Group, Cancer Research UK, Paterson Institute for Cancer Research, The University of Manchester, Manchester, UK.
Mol Syst Biol. 2011 Dec 20;7:559. doi: 10.1038/msb.2011.90.
Strand-specific RNA sequencing of S. pombe revealed a highly structured programme of ncRNA expression at over 600 loci. Waves of antisense transcription accompanied sexual differentiation. A substantial proportion of ncRNA arose from mechanisms previously considered to be largely artefactual, including improper 3' termination and bidirectional transcription. Constitutive induction of the entire spk1+, spo4+, dis1+ and spo6+ antisense transcripts from an integrated, ectopic, locus disrupted their respective meiotic functions. This ability of antisense transcripts to disrupt gene function when expressed in trans suggests that cis production at native loci during sexual differentiation may also control gene function. Consistently, insertion of a marker gene adjacent to the dis1+ antisense start site mimicked ectopic antisense expression in reducing the levels of this microtubule regulator and abolishing the microtubule-dependent 'horsetail' stage of meiosis. Antisense production had no impact at any of these loci when the RNA interference (RNAi) machinery was removed. Thus, far from being simply 'genome chatter', this extensive ncRNA landscape constitutes a fundamental component in the controls that drive the complex programme of sexual differentiation in S. pombe.
秀丽隐杆线虫特异性 RNA 测序揭示了超过 600 个基因座中 ncRNA 表达的高度结构化程序。反义转录伴随着性分化而出现。大量的 ncRNA 来自于先前被认为主要是人为因素的机制，包括不正确的 3' 终止和双向转录。从一个整合的、异位的、基因座中诱导整个 spk1+、spo4+、dis1+ 和 spo6+ 反义转录本，破坏了它们各自的减数分裂功能。这些反义转录本在表达时能够破坏基因功能的能力表明，在性分化过程中，顺式在天然基因座上的产生也可能控制基因功能。一致地，将一个标记基因插入到 dis1+ 反义起始位点附近，模拟了异位反义表达，降低了这种微管调节剂的水平，并消除了减数分裂中微管依赖性的“马尾”阶段。当 RNA 干扰 (RNAi) 机制被去除时，在这些基因座中的任何一个基因座中，反义产物都没有影响。因此，这种广泛的 ncRNA 景观远非简单的“基因组闲聊”，而是构成了秀丽隐杆线虫复杂的性分化控制程序的一个基本组成部分。
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