Schlissel Gavin, Krzyzanowski Marek K, Caudron Fabrice, Barral Yves, Rine Jasper
Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA 94720, USA.
Institute of Biochemistry, ETH Zürich, Zürich, Switzerland.
Science. 2017 Mar 17;355(6330):1184-1187. doi: 10.1126/science.aaj2103. Epub 2017 Mar 16.
In yeast, heterochromatin silencing is reported to decline in aging mother cells, causing sterility in old cells. This process is thought to reflect a decrease in the activity of the NAD (oxidized nicotinamide adenine dinucleotide)-dependent deacetylase Sir2. We tested whether Sir2 becomes nonfunctional gradually or precipitously during aging. Unexpectedly, silencing of the heterochromatic and loci was not lost during aging. Old cells could initiate a mating response; however, they were less sensitive to mating pheromone than were young cells because of age-dependent aggregation of Whi3, an RNA-binding protein controlling S-phase entry. Removing the polyglutamine domain of Whi3 restored the pheromone sensitivity of old cells. We propose that aging phenotypes previously attributed to loss of heterochromatin silencing are instead caused by aggregation of the Whi3 cell cycle regulator.
据报道，在酵母中，衰老母细胞的异染色质沉默作用会减弱，导致老细胞不育。这一过程被认为反映了依赖烟酰胺腺嘌呤二核苷酸（NAD，氧化型辅酶Ⅰ）的去乙酰化酶Sir2的活性降低。我们测试了Sir2在衰老过程中是逐渐失去功能还是突然失去功能。出乎意料的是，异染色质和位点的沉默在衰老过程中并未丧失。老细胞能够启动交配反应；然而，由于控制S期进入的RNA结合蛋白Whi3随年龄增长而聚集，它们对交配信息素的敏感性低于年轻细胞。去除Whi3的聚谷氨酰胺结构域可恢复老细胞对信息素的敏感性。我们提出，以前归因于异染色质沉默丧失的衰老表型，实际上是由Whi3细胞周期调节因子的聚集引起的。
