Effect of the autism‐associated lncRNA Shank2‐AS on architecture and growth of neurons

• Published in: Journal of cellular biochemistry Vol. 120; no. 2; pp. 1754 - 1762
• Main Authors: Luo, Ting, Liu, Ping, Wang, Xiao‐Yan, Li, Le‐Zhi, Zhao, Li‐Ping, Huang, Jin, Li, Ya‐Min, Ou, Jin‐Lan, Peng, Xiao‐Qing
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2019
• Subjects: Ankyrins; Antisense RNA; Apoptosis; Autism; Cell proliferation; Domains; Gene expression; long noncoding RNA; neuron; Neurons; Patients; Ribonucleic acid; RNA; Shank2‐AS; siRNA; Transfection; Shank2-AS; long noncoding RNA; neuron; autism
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.27471

The pathogenic mechanism of autism is complex, and current research has shown that long noncoding RNAs (lncRNAs) may play important roles in this process. The antisense lncRNA of SH3 and multiple ankyrin repeat domains 2 (Shank2‐AS) is upregulated in patients with autism spectrum disorder (ASD), whereas the expression of its sense strand gene Shank2 is downregulated. In neuronal cells, Shank2‐AS and Shank2 can form a double‐stranded RNA and inhibit Shank2 expression. Overexpression of Shank2‐AS decreases neurite numbers and lengths, thereby inhibiting the proliferation of neuronal cells and promoting their apoptosis. Overexpression of Shank2 inhibits the abovementioned effects of Shank2‐AS, and transfection of a vector containing the 10th intron of Shank2 (Shank2‐AS is reverse‐transcribed from this region) also blocks the function of Shank2‐AS. Shank2 small interfering RNA plays a role similar to Shank2‐AS. Therefore, Shank2‐AS is abnormally expressed in patients with ASD and may affect the structure and growth of neurons by regulating Shank2 expression, thereby facilitating the development of ASD. Shank2‐AS expression was negatively correlated with Shank2 expression in autism spectrum disorder patients. Shank2‐AS binds Shank2 messenger RNA and regulates its expression. Overexpression of Shank2‐AS decreases neurite numbers and lengths. Shank2‐AS overexpression inhibits neuron proliferation and promotes its apoptosis.