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
Department of Medical Genetics, School of Basic Medical Sciences, Nanjing Medical University, Jiangsu, 211166, Nanjing, P. R. China.
Department of Medical Genetics, Children's Hospital and Clinics of Minnesota, Minneapolis, MI, 55404, USA.
Cell Biosci. 2021 Mar 2;11(1):47. doi: 10.1186/s13578-021-00559-8.
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.
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.
This work demonstrates that DNM3OS is essential for preventing premature differentiation of chondrocytes required for bone growth through endochondral ossification.
骨骼发育和维持是复杂的过程，已知由多种遗传和表观遗传信号通路协调。然而，长链非编码RNA（lncRNA）作为一类关键的表观遗传调控分子，在骨骼生物学中的作用尚未得到充分研究。
在此，我们报告了一名身材矮小、下丘脑功能障碍和轻度巨头畸形的年轻患者，其携带母系遗传的1号染色体q24.2区域690 kb的缺失，该区域包含一个非编码RNA基因DNM3OS，它反向嵌入动力蛋白3（DNM3）基因的一个内含子中。我们发现lncRNA DNM3OS可独立于两个共顺反子微小RNA miR-199a和miR-214维持软骨细胞的增殖。我们进一步表明，神经生长因子（NGF）作为软骨细胞生长的已知因子，是DNM3OS介导的软骨细胞增殖调控的关键靶点。
这项研究表明，DNM3OS对于防止通过软骨内成骨进行骨生长所需的软骨细胞过早分化至关重要。
