Senescence-associated Long Non-coding RNA (SALNR) Delays Oncogene-induced Senescence through NF90 Regulation.
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.
From the Department of Biochemistry and Molecular Biology and Beijing Key Laboratory for "Posttranslational Modification and Cellular Function," Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Cheng-Lin
CL
Wu
the Departments of Urology and Microbiology, New York University Medical Center, New York, New York 10016, and.
Yu
Y
Wang
From the Department of Biochemistry and Molecular Biology and Beijing Key Laboratory for "Posttranslational Modification and Cellular Function," Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Bo
B
Jin
From the Department of Biochemistry and Molecular Biology and Beijing Key Laboratory for "Posttranslational Modification and Cellular Function," Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Hao
H
Chen
the Department of Gastroenterology, First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang 330000, China.
Bu-Shan
BS
Xie
From the Department of Biochemistry and Molecular Biology and Beijing Key Laboratory for "Posttranslational Modification and Cellular Function," Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191, China, zbmao@bjmu.edu.cn.
Ze-Bin
ZB
Mao
D002466:Cell Nucleolus / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D050779:Nuclear Factor 90 Proteins / Q000502:physiology*; D009857:Oncogenes; D021381:Protein Transport; D062085:RNA, Long Noncoding / Q000235:genetics*
C429643:ILF3 protein, human; D050779:Nuclear Factor 90 Proteins; D062085:RNA, Long Noncoding
NF90; Ras protein; SALNR; aging; long noncoding RNA (long ncRNA, lncRNA); oncogene; senescence