德国科隆大学生物物理研究所Tobias Bollenbach研究小组近期取得重要工作进展。他们研究发现了内含子介导的表型异质性诱导。这一研究成果2022年4月20日在线发表于《自然》杂志上。
在这里，通过将等生长分析与单细胞蛋白质检测相结合，研究人员发现内含子可以介导可诱导的表型异质性，从而具有明显的适应性优势。渗透胁迫导致小核糖体亚基蛋白Rps22B的双峰表达，这是由其转录本5'非翻译区的内含子介导的。由此产生的两个酵母亚群应对饥饿的能力有所不同。低水平的Rps22B蛋白可以延长细胞在持续饥饿下的存活时间，而高水平的Rps22B可以使细胞在短暂饥饿后生长更快。
此外，与成熟葡萄中的酵母类似，在高浓度糖环境下生长的酵母在接近稳定期时表现出Rps22B的双峰表达。当在自然环境中受到饥饿威胁时，核糖体蛋白基因的差异内含子介导的调节提供了一种使种群多样化的方法。他们的研究结果揭示了内含子在不断变化的环境中诱导表型异质性的作用，并表明酵母中重复的核糖体蛋白基因有助于解决精确表达控制和环境反应之间的进化冲突。
据悉，在RNA转录成熟过程中被移除的基因内区域（内含子）普遍存在于真核生物的核基因组中。芽殖酵母是一种缺乏内含子的物种，它保留了两组核糖体蛋白基因，它们的主要差异在于它们的内含子。尽管研究已经阐明了核糖体蛋白内含子在应激和饥饿条件下的作用，但了解内含子对核糖体调控的贡献仍然具有挑战性。
附：英文原文
Title: Intron-mediated induction of phenotypic heterogeneity
Author: Lukaiin, Martin, Espinosa-Cant, Adriana, Bollenbach, Tobias
Issue&Volume: 2022-04-20
Abstract: Intragenic regions that are removed during maturation of the RNA transcript—introns—are universally present in the nuclear genomes of eukaryotes1. The budding yeast, an otherwise intron-poor species, preserves two sets of ribosomal protein genes that differ primarily in their introns2,3. Although studies have shed light on the role of ribosomal protein introns under stress and starvation4,5,6, understanding the contribution of introns to ribosome regulation remains challenging. Here, by combining isogrowth profiling7 with single-cell protein measurements8, we show that introns can mediate inducible phenotypic heterogeneity that confers a clear fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal subunit protein Rps22B, which is mediated by an intron in the 5′ untranslated region of its transcript. The two resulting yeast subpopulations differ in their ability to cope with starvation. Low levels of Rps22B protein result in prolonged survival under sustained starvation, whereas high levels of Rps22B enable cells to grow faster after transient starvation. Furthermore, yeasts growing at high concentrations of sugar, similar to those in ripe grapes, exhibit bimodal expression of Rps22B when approaching the stationary phase. Differential intron-mediated regulation of ribosomal protein genes thus provides a way to diversify the population when starvation threatens in natural environments. Our findings reveal a role for introns in inducing phenotypic heterogeneity in changing environments, and suggest that duplicated ribosomal protein genes in yeast contribute to resolving the evolutionary conflict between precise expression control and environmental responsiveness9.
DOI: 10.1038/s41586-022-04633-0
Source: https://www.nature.com/articles/s41586-022-04633-0
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
