Rodrigues Joana, Lydall David
Institute for Cell and Molecular Biosciences, Newcastle University Medical School, Newcastle upon Tyne, NE2 4HH, UK.
Curr Genet. 2018 Oct;64(5):1105-1116. doi: 10.1007/s00294-018-0828-6. Epub 2018 Mar 22.
Saccharomyces cerevisiae is a commonly used model organism for understanding eukaryotic gene function. However, the close proximity between yeast genes can complicate the interpretation of yeast genetic data, particularly high-throughput data. In this study, we examined the interplay between genes encoding components of the PAF1 complex and VPS36, the gene located next to CDC73 on chromosome XII. The PAF1 complex (Cdc73, Paf1, Ctr9, Leo1, and Rtf1, in yeast) affects RNA levels by affecting transcription, histone modifications, and post-transcriptional RNA processing. The human PAF1 complex is linked to cancer, and in yeast, it has been reported to play a role in telomere biology. Vps36, part of the ESCRT-II complex, is involved in sorting proteins for vacuolar/lysosomal degradation. We document a complex set of genetic interactions, which include an adjacent gene effect between CDC73 and VPS36 and synthetic sickness between vps36Δ and cdc73Δ, paf1Δ, or ctr9Δ. Importantly, paf1Δ and ctr9Δ are synthetically lethal with deletions of other components of the ESCRT-II (SNF8 and VPS25), ESCRT-I (STP22), or ESCRT-III (SNF7) complexes. We found that RNA levels of VPS36, but not other ESCRT components, are positively regulated by all components of the PAF1 complex. Finally, we show that deletion of ESCRT components decreases the telomere length in the S288C yeast genetic background, but not in the W303 background. Together, our results outline complex interactions, in cis and in trans, between genes encoding PAF1 and ESCRT-II complex components that affect telomere function and cell viability in yeast.
酿酒酵母是用于理解真核基因功能的常用模式生物。然而，酵母基因之间的紧密相邻可能会使酵母遗传数据的解释变得复杂，尤其是高通量数据。在本研究中，我们研究了编码PAF1复合物组分的基因与VPS36之间的相互作用，VPS36是位于第十二号染色体上紧邻CDC73的基因。PAF1复合物（在酵母中为Cdc73、Paf1、Ctr9、Leo1和Rtf1）通过影响转录、组蛋白修饰和转录后RNA加工来影响RNA水平。人类PAF1复合物与癌症有关，并且在酵母中，据报道它在端粒生物学中发挥作用。Vps36是ESCRT-II复合物的一部分，参与将蛋白质分类以便进行液泡/溶酶体降解。我们记录了一组复杂的遗传相互作用，其中包括CDC73和VPS36之间的相邻基因效应以及vps36Δ与cdc73Δ、paf1Δ或ctr9Δ之间的合成病性。重要的是，paf1Δ和ctr9Δ与ESCRT-II（SNF8和VPS25）、ESCRT-I（STP22）或ESCRT-III（SNF7）复合物的其他组分的缺失是合成致死的。我们发现VPS36的RNA水平，而不是其他ESCRT组分的RNA水平，受到PAF1复合物所有组分的正向调节。最后，我们表明ESCRT组分的缺失会降低S288C酵母遗传背景下的端粒长度，但在W303背景下则不会。总之，我们的结果概述了编码PAF1和ESCRT-II复合物组分的基因之间顺式和反式的复杂相互作用，这些相互作用影响酵母中的端粒功能和细胞活力。
