Panoramic transcriptome analysis and functional screening of long noncoding RNAs in mouse spermatogenesis

Kai Li # 1, Jiayue Xu # 1, Yanyun Luo # 1, Dingfeng Zou 1, Ruiqin Han 1, Shunshun Zhong 1, Qing Zhao 1, Xinyu Mang 1, Mengzhen Li 1, Yanmin Si 1, Yan Lu 1, Pengyu Li 1, Cheng Jin 1, Zhipeng Wang 1, Fang Wang 1, Shiying Miao 1, Bo Wen 2, Linfang Wang 1, Yanni Ma 1, Jia Yu 1, Wei Song 1

Genome Res. 2021 Jan;31(1):13-26. doi: 10.1101/gr.264333.

PMID: 33328167

Abstract

Long noncoding RNAs (lncRNAs) have emerged as diverse functional regulators involved in mammalian development; however, large-scale functional investigation of lncRNAs in mammalian spermatogenesis in vivo is lacking. Here, we delineated the global lncRNA expression landscape in mouse spermatogenesis and identified 968 germ cell signature lncRNAs. By combining bioinformatics and functional screening, we identified three functional lncRNAs (Gm4665, 1700027A15Rik, and 1700052I22Rik) that directly influence spermatogenesis in vivo. Knocking down Gm4665 hampered the development of round spermatids into elongating spermatids and disrupted key spermatogenic gene expression. Mechanistically, lncRNA Gm4665 localized in the nucleus of round spermatids and occupied the genomic regulatory region of important spermatogenic genes including Ip6k1 and Akap3 These findings provide a valuable resource and framework for future functional analysis of lncRNAs in spermatogenesis and their potential roles in other biological processes.