Senescence-associated Long Non-coding RNA (SALNR) Delays Oncogene-induced Senescence through NF90 Regulation

• Published in: The Journal of biological chemistry Vol. 290; no. 50; pp. 30175 - 30192
• Main Authors: Wu, Cheng-Lin, Wang, Yu, Jin, Bo, Chen, Hao, Xie, Bu-Shan, Mao, Ze-Bin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.12.2015; American Society for Biochemistry and Molecular Biology
• Subjects: aging; Cell Biology; Cell Nucleolus - metabolism; Cells, Cultured; Cellular Senescence - genetics; Genome-Wide Association Study; Humans; long noncoding RNA (long ncRNA, lncRNA); NF90; Nuclear Factor 90 Proteins - physiology; oncogene; Oncogenes; Protein Transport; Ras protein; RNA, Long Noncoding - genetics; SALNR; senescence; senescence; SALNR; long noncoding RNA (long ncRNA, lncRNA); Ras protein; aging; NF90; oncogene
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M115.661785

Long non-coding RNAs (lncRNAs) have recently emerged as key players in many physiologic and pathologic processes. Although many lncRNAs have been identified, few lncRNAs have been characterized functionally in aging. In this study, we used human fibroblast cells to investigate genome-wide lncRNA expression during cellular senescence. We identified 968 down-regulated lncRNAs and 899 up-regulated lncRNAs in senescent cells compared with young cells. Among these lncRNAs, we characterized a senescence-associated lncRNA (SALNR), whose expression was reduced during cellular senescence and in premalignant colon adenomas. Overexpression of SALNR delayed cellular senescence in fibroblast cells. Furthermore, we found that SALNR interacts with NF90 (nuclear factor of activated T-cells, 90 kDa), an RNA-binding protein suppressing miRNA biogenesis. We demonstrated that NF90 is a SALNR downstream target, whose inhibition led to premature senescence and enhanced expressions of senescence-associated miRNAs. Moreover, our data showed that Ras-induced stress promotes NF90 nucleolus translocation and suppresses its ability to suppress senescence-associated miRNA biogenesis, which could be rescued by SALNR overexpression. These data suggest that lncRNA SALNR modulates cellular senescence at least partly through changing NF90 activity. Background: The role of long non-coding RNAs (lncRNAs) in senescence is little known. Results: Senescence-associated lncRNA (SALNR) expression is reduced during senescence. SALNR delays oncogene-induced senescence through suppressing NF90 nucleolus translocation. Conclusion: lncRNA SALNR plays an important role in senescence. Significance: We profiled lncRNAs in senescence and provided novel insights into the role of lncRNAs in senescence.