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

Autor: Qiu fan Xu, Chen Liu, Sarah L. Dugan, Huai ze Liu, Betsy A. Hirsch, Hui jie Huang, Xiao tong Liu, Jennifer Roggenbuck, Ting ting Yu, Steven Y. Cheng, Shen Yue, Si Yang Li, Lei Shao
Rok vydání: 2021
Předmět:
Zdroj: Cell & Bioscience, Vol 11, Iss 1, Pp 1-15 (2021)
Cell & Bioscience
ISSN: 2045-3701
DOI: 10.1186/s13578-021-00559-8
Popis: Background Skeletal 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. Results Here 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. Conclusions This work demonstrates that DNM3OS is essential for preventing premature differentiation of chondrocytes required for bone growth through endochondral ossification.
Databáze: OpenAIRE
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