长链非编码 RNA Uhg4 在果蝇中的多效适应性效应。

Pleiotropic fitness effects of the lncRNA Uhg4 in Drosophila melanogaster.

机构信息

Center for Human Genetics and Department of Genetics and Biochemistry, Clemson University, 114 Gregor Mendel Circle, Greenwood, SC, 29646, USA.

Present adress: Clemson Veterinary Diagnostic Center, Livestock Poultry Health, Clemson University, 500 Clemson Road, Columbia, SC, 29229, USA.

出版信息

BMC Genomics. 2022 Nov 30;23(1):781. doi: 10.1186/s12864-022-08972-0.

DOI:10.1186/s12864-022-08972-0

PMID:36451091

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9710044/

Abstract

BACKGROUND

Long noncoding RNAs (lncRNAs) are a diverse class of RNAs that are critical for gene regulation, DNA repair, and splicing, and have been implicated in development, stress response, and cancer. However, the functions of many lncRNAs remain unknown. In Drosophila melanogaster, U snoRNA host gene 4 (Uhg4) encodes an antisense long noncoding RNA that is host to seven small nucleolar RNAs (snoRNAs). Uhg4 is expressed ubiquitously during development and in all adult tissues, with maximal expression in ovaries; however, it has no annotated function(s).

RESULTS

We used CRISPR-Cas9 germline gene editing to generate multiple deletions spanning the promoter region and first exon of Uhg4. Females showed arrested egg development and both males and females were sterile. In addition, Uhg4 deletion mutants showed delayed development and decreased viability, and changes in sleep and responses to stress. Whole-genome RNA sequencing of Uhg4 deletion flies and their controls identified co-regulated genes and genetic interaction networks associated with Uhg4. Gene ontology analyses highlighted a broad spectrum of biological processes, including regulation of transcription and translation, morphogenesis, and stress response.

CONCLUSION

Uhg4 is a lncRNA essential for reproduction with pleiotropic effects on multiple fitness traits.

摘要

背景

长非编码 RNA（lncRNA）是一类重要的 RNA，在基因调控、DNA 修复和剪接中发挥着关键作用，并且与发育、应激反应和癌症有关。然而，许多 lncRNA 的功能仍然未知。在黑腹果蝇中，U snoRNA 宿主基因 4（Uhg4）编码一种反义长非编码 RNA，该 RNA 是七个小核仁 RNA（snoRNA）的宿主。Uhg4 在发育过程中以及所有成年组织中广泛表达，在卵巢中表达最高；然而，它没有注释的功能。

结果

我们使用 CRISPR-Cas9 生殖系基因编辑技术生成了跨越 Uhg4 启动子区域和第一外显子的多个缺失突变体。雌性表现出卵发育停滞，雄性和雌性均不育。此外，Uhg4 缺失突变体表现出发育迟缓、活力下降、睡眠改变和对压力的反应变化。Uhg4 缺失突变体和对照的全基因组 RNA 测序鉴定了与 Uhg4 相关的共调控基因和遗传相互作用网络。基因本体分析突出了广泛的生物学过程，包括转录和翻译调控、形态发生和应激反应。