A long noncoding RNA binding to QKI-5 regulates germ cell apoptosis via p38 MAPK signaling pathway

• Published in: Cell death & disease 2019-09, Vol.10 (10), p.699-14, Article 699
• Main Authors: Li, Kai, Zhong, Shunshun, Luo, Yanyun, Zou, Dingfeng, Li, Mengzhen, Li, Yahui, Lu, Yan, Miao, Shiying, Wang, Linfang, Song, Wei
• Format: Article
• Language: English
• Subjects: 13/1; 13/2; 13/31; 13/89; 14/19; 14/34; 38/44; 38/61; 38/77; 38/89; 45/61; 45/90; 631/136/2434/1822; 631/337/384/2568; 82/29; Animals; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell activation; Cell Biology; Cell Culture; DNA microarrays; Germ Cells - metabolism; Humans; Immunology; Immunoprecipitation; Life Sciences; Male; MAP kinase; MAP Kinase Signaling System - genetics; Mice; Phenotypes; Qk protein; Ribonucleic acid; RNA; RNA, Long Noncoding - metabolism; RNA-Binding Proteins - metabolism; Signal Transduction; Spermatocytes; Spermatogenesis; Spermatogenesis - genetics; Spermatogonia
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1941-2

Spermatogenesis is the complex process of male germline development and requires coordinated interactions by multiple gene products that undergo strict developmental regulations. Increasing evidence has suggested that a number of long noncoding RNAs (lncRNAs) may function as important regulatory molecules in various physiological and pathological processes by binding to specific proteins. Here, we identified a subset of QKI-5-binding lncRNAs in the mouse testis through the integrated analyses of RNA immunoprecipitation (RIP)-microarray and biological verification. Among the lncRNAs, we revealed that NONMMUT074098.2 ( Lnc10 ), which was highly expressed in the spermatogonia and spermatocytes of the testis, interacted with QKI-5. Furthermore, Lnc10 depletion promoted germ cell apoptosis via the activation of p38 MAPK, whereas the simultaneous knockdown of QKI-5 could rescue the apoptotic phenotype and the activation of p38 MAPK, which were induced by the loss of Lnc10 . These data indicated that the Lnc10 -QKI-5 interaction was associated with the regulatory roles of QKI-5 and that the Lnc10 -QKI-5 interaction inhibited the regulation of QKI-5 on the downstream p38 MAPK signaling pathway. Additionally, we functionally characterized the biological roles of Lnc10 and found that the knockdown of Lnc10 promoted the apoptosis of spermatogenic cells in vivo; this suggested that Lnc10 had an important biological role in mouse spermatogenesis. Thus, our study provides a potential strategy to investigate the biological significance of lncRNA-RBP interactions during male germline development.