关键词: epigenetics gene regulation heredity operon poly-UG RNAs transgenerational gene silencing

来  源:   DOI:10.1101/2024.04.28.591487   PDF(Pubmed)

Abstract:
Heritable gene silencing has been proposed to rely on DNA methylation, histone modifications, and/or non-coding RNAs in different organisms. Here we demonstrate that multiple RNA-mediated mechanisms with distinct and easily detectable molecular signatures can underlie heritable silencing of the same open-reading frame in the nematode C. elegans. Using two-gene operons, we reveal three cases of gene-selective silencing that provide support for the transmission of heritable epigenetic changes through different mechanisms of RNA silencing independent of changes in chromatin that would affect all genes of an operon equally. Different heritable epigenetic states of a gene were associated with distinct populations of stabilized mRNA fragments with untemplated poly-UG (pUG) tails, which are known intermediates of RNA silencing. These \'pUG signatures\' provide a way to distinguish the multiple mechanisms that can drive heritable RNA silencing of a single gene.
摘要:
已提出可遗传基因沉默依赖于DNA甲基化,组蛋白修饰,和/或非编码RNA在不同的生物体。在这里,我们证明了具有不同且易于检测的分子特征的多种RNA介导的机制可以成为线虫C.elegans中相同开放阅读框的可遗传沉默的基础。使用双基因操纵子,我们揭示了3例基因选择性沉默,这些基因选择性沉默通过不同的RNA沉默机制为遗传表观遗传变化的传播提供了支持,而与染色质变化无关,染色质变化会对操纵子的所有基因产生同等影响.基因的不同遗传表观遗传状态与不同的稳定mRNA片段种群相关,这些片段具有未模板化的聚UG(pUG)尾巴,它们是已知的RNA沉默的中间体。这些“pUG签名”提供了一种区分多种机制的方法,这些机制可以驱动单个基因的可遗传RNA沉默。
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