期刊
GENOME BIOLOGY
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13059-020-02081-5
关键词
Tug1; lncRNA; Fertility; DNA repressor; Cis-regulatory elements; RNA-seq; Allele-specific; Genetics; Genomics; Mouse
资金
- Blavatnik Accelerator Program [P01GM099117]
- Harvard Initiative for RNA Medicine
- National Institutes of Health (NIH) General Medical Sciences [1F32GM122335-01A1]
Background Several long noncoding RNAs (lncRNAs) have been shown to function as components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, studying lncRNA function has been a challenge due to their diverse biological roles and because lncRNA loci can contain multiple molecular modes that may exert function. Results We previously generated and characterized a cohort of 20 lncRNA loci knockout mice. Here, we extend this initial study and provide a more detailed analysis of the highly conserved lncRNA locus, taurine-upregulated gene 1 (Tug1). We report that Tug1-knockout male mice are sterile with underlying defects including a low number of sperm and abnormal sperm morphology. Because lncRNA loci can contain multiple modes of action, we wanted to determine which, if any, potential elements contained in the Tug1 genomic region have any activity. Using engineered mouse models and cell-based assays, we provide evidence that the Tug1 locus harbors two distinct noncoding regulatory activities, as acis-DNA repressor that regulates neighboring genes and as a lncRNA that can regulate genes by atrans-based function. We also show that Tug1 contains an evolutionary conserved open reading frame that when overexpressed produces a stable protein which impacts mitochondrial membrane potential, suggesting a potential third coding function. Conclusions Our results reveal an essential role for the Tug1 locus in male fertility and uncover evidence for distinct molecular modes in the Tug1 locus, thus highlighting the complexity present at lncRNA loci.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据