tRNA-derived small non-coding RNAs perturb C. elegans gene expression in response to genotoxic stress.

Research shows that the individual lifestyle and environment of an organism can influence its phenotype and potentially the phenotype of its offspring. The different genetic and non-genetic components of the inheritance system and their mutual interactions are key mechanisms to generate inherited phenotypic changes. Epigenetic changes can be transmitted between generations independently from changes in DNA sequence. In C. elegans, epigenetic differences, i.e., epimutations, mediated by small non-coding RNAs, particularly 22G RNAs, as well as chromatin have been identified and their average persistence is 3 to 5 generations. In addition, previous research showed that some epimutations had a longer duration and concerned genes that were enriched for multiple components of xenobiotic response pathways. These results raise the possibility that environmental stresses might change the rate at which epimutations occur, with potential significance for adaptation. In this work, we explore this question by propagating C. elegans lines either in control conditions or in moderate or high doses of the chemical cisplatin, which introduces genotoxic stress by damaging DNA. Our results show that cisplatin has a limited effect on global small non-coding RNAs epimutations but does affect epimutation rate on tRNAs 3 prime halves. Such changes in tRNAs fragments may impact genes expression. This result echo recent advances in environmental epigenetic suggesting tRNAs as potentials new epigenetic regulators in multi/transgenerational inheritance and offspring adaptation.

研究表明，生物体的个体生活方式与所处环境能够影响其自身表型，亦可能对子代表型产生影响。遗传系统中各类遗传与非遗传组分及其相互作用，是介导可遗传表型改变的核心机制。表观遗传（epigenetic）改变可脱离DNA序列变异，在代际间传递。在秀丽隐杆线虫（C. elegans）中，研究人员已鉴定出由小分子非编码RNA（small non-coding RNAs，尤其是22G RNA）以及染色质（chromatin）介导的表观遗传差异，即表观突变（epimutation），这类突变的平均持续时长为3至5个世代。此外，既往研究显示，部分表观突变的持续时长更长，且相关基因富集有异生物应答通路（xenobiotic response pathways）的多种组分。上述结果提示，环境应激可能会改变表观突变的发生频率，这或许对生物的适应性具有重要意义。本研究通过将秀丽隐杆线虫品系分别培养于对照条件、中等剂量或高剂量的顺铂（cisplatin）环境中展开相关探究——顺铂可通过损伤DNA引入遗传毒性应激（genotoxic stress）。研究结果表明，顺铂对全局小分子非编码RNA表观突变的影响较为有限，但确实会影响转运RNA（tRNA）3'端片段的表观突变频率。这类tRNA片段的改变可能会影响基因的表达。该结果与近期环境表观遗传学的研究进展相呼应，提示tRNA可能是跨代遗传与子代适应过程中一类潜在的新型表观遗传调控因子。