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- Title
Deletion at an 1q24 locus reveals a critical role of long noncoding RNA DNM3OS in skeletal development.
- Authors
Yu, Ting-ting; Xu, Qiu-fan; Li, Si-Yang; Huang, Hui-jie; Dugan, Sarah; Shao, Lei; Roggenbuck, Jennifer A.; Liu, Xiao-tong; Liu, Huai-ze; Hirsch, Betsy A.; Yue, Shen; Liu, Chen; Cheng, Steven Y.
- Abstract
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.
- Subjects
NEUROTROPHINS; LINCRNA; NON-coding RNA; SHORT stature; BONE growth; GENES; ENDOCHONDRAL ossification; BIOLOGY
- Publication
Cell & Bioscience, 2021, Vol 11, Issue 1, p1
- ISSN
2045-3701
- Publication type
Article
- DOI
10.1186/s13578-021-00559-8