Individual long non-coding RNAs have no overt functions in zebrafish embryogenesis, viability and fertility

Individual long non-coding RNAs have no overt functions in zebrafish embryogenesis, viability and fertility
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DOI:
10.7554/elife.40815
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发表时间:
2019-01-08
期刊:
影响因子:
7.7
通讯作者:
Schier, Alexander F.
Schier, Alexander F.
中科院分区:
生物学1区
文献类型:
--
作者:
Goudarzi, Mehdi;Berg, Kathryn;Schier, Alexander F.

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数百种长链非编码RNA(lncRNA)已被鉴定为基因表达的潜在调节因子,但它们的功能在很大程度上仍然未知。为了研究lncRNA在脊椎动物发育过程中的作用,我们基于其保守性、表达谱或与发育调节因子的接近性选择了25种斑马鱼lncRNA,并使用CRISPR-Cas9产生了32个缺失等位基因。我们在一些突变体中观察到邻近基因的转录改变,但没有一个lncRNA是胚胎发生、生存力或生育力所必需的。甚至先前提出的非编码功能的RNA(cyrano和squint)和其他保守的lncRNA(gas 5和lnc-setd 1ba)也被排除在外。在一种情况下(lnc-phox 2bb),缺乏推定的DNA调控元件,但不是lncRNA转录本本身,导致异常发育。lncRNA可能有冗余的,微妙的,或上下文依赖的作用,但从我们的研究结果外推表明,大多数个体斑马鱼lncRNA在胚胎发生,活力和生育力没有明显的作用。
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 (cyrano and squint) and other conserved lncRNAs (gas5 and lnc-setd1ba) were dispensable. In one case (lnc-phox2bb), 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.