Deletion at an 1q24 locus reveals a critical role of long noncoding RNA DNM3OS in skeletal development

Cell & Bioscience

Sarah Dugan¹  Chen Liu²  Steven Y. Cheng²  Huai-ze Liu²  Si-Yang Li²  Shen Yue²  Ting-ting Yu²  Qiu-fan Xu²  Xiao-tong Liu²  Lei Shao²  Hui-jie Huang²  Jennifer A. Roggenbuck³  Betsy A. Hirsch⁴ 

[1] Department of Medical Genetics, Children’s Hospital and Clinics of Minnesota, 55404, Minneapolis, MI, USA;Department of Medical Genetics, School of Basic Medical Sciences, Nanjing Medical University, 211166, Nanjing, Jiangsu, P. R. China;Department of Neurology, Ohio State University Medical Center, 43210, Columbus, OH, USA;University of Minnesota Medical Center-Fairview, 55404, Minneapolis, MI, USA;

关键词: Skeletal abnormalities;    1q24;    lncRNA;    DNM3OS;    Nerve growth factor;   

DOI  :  10.1186/s13578-021-00559-8

来源: Springer

【 摘 要 】

BackgroundSkeletal development and maintenance are complex processes known to be coordinated by multiple genetic and epigenetic signaling pathways. However, the role of long non-coding RNAs (lncRNAs), a class of crucial epigenetic regulatory molecules, has been under explored in skeletal biology.ResultsHere we report a young patient with short stature, hypothalamic dysfunction and mild macrocephaly, who carries a maternally inherited 690 kb deletion at Chr.1q24.2 encompassing a noncoding RNA gene, DNM3OS, embedded on the opposite strand in an intron of the DYNAMIN 3 (DNM3) gene. We show that lncRNA DNM3OS sustains the proliferation of chondrocytes independent of two co-cistronic microRNAs miR-199a and miR-214. We further show that nerve growth factor (NGF), a known factor of chondrocyte growth, is a key target of DNM3OS-mediated control of chondrocyte proliferation.ConclusionsThis work demonstrates that DNM3OS is essential for preventing premature differentiation of chondrocytes required for bone growth through endochondral ossification.

【 授权许可】

CC BY