Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
Center for Brain Science, Harvard University, Cambridge, United States.
Elife. 2019 Jan 8;8:e40815. doi: 10.7554/eLife.40815.
Hundreds of long non-coding RNAs (lncRNAs) have been identified as potential regulators of gene expression, but their functions remain largely unknown. To study the role of lncRNAs during vertebrate development, we selected 25 zebrafish lncRNAs based on their conservation, expression profile or proximity to developmental regulators, and used CRISPR-Cas9 to generate 32 deletion alleles. We observed altered transcription of neighboring genes in some mutants, but none of the lncRNAs were required for embryogenesis, viability or fertility. Even RNAs with previously proposed non-coding functions ( and ) and other conserved lncRNAs ( and were dispensable. In one case (), absence of putative DNA regulatory-elements, but not of the lncRNA transcript itself, resulted in abnormal development. LncRNAs might have redundant, subtle, or context-dependent roles, but extrapolation from our results suggests that the majority of individual zebrafish lncRNAs have no overt roles in embryogenesis, viability and fertility.
数百个长非编码 RNA(lncRNA)已被鉴定为潜在的基因表达调控因子,但它们的功能仍知之甚少。为了研究 lncRNA 在脊椎动物发育过程中的作用,我们根据它们的保守性、表达谱或与发育调节剂的接近程度,选择了 25 个斑马鱼 lncRNA,并使用 CRISPR-Cas9 生成了 32 个缺失等位基因。我们观察到一些突变体中邻近基因的转录发生改变,但没有一个 lncRNA 是胚胎发生、生存或生育所必需的。即使是具有先前提出的非编码功能的 RNA( 和 )和其他保守的 lncRNA( 和 )也是可有可无的。在一种情况下(),缺失假定的 DNA 调控元件,但不是 lncRNA 转录本本身,导致发育异常。lncRNA 可能具有冗余的、微妙的或依赖于上下文的作用,但从我们的结果推断,大多数单个斑马鱼 lncRNA 在胚胎发生、生存和生育方面没有明显的作用。