Long non‐coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling

• Published in: EMBO molecular medicine Vol. 8; no. 4; pp. 346 - 362
• Main Authors: Yao, Jin, Wang, Xiao‐Qun, Li, Yu‐Jie, Shan, Kun, Yang, Hong, Wang, Yang‐Ning‐Zhi, Yao, Mu‐Di, Liu, Chang, Li, Xiu‐Miao, Shen, Yi, Liu, Jing‐Yu, Cheng, Hong, Yuan, Jun, Zhang, Yang‐Yang, Jiang, Qin, Yan, Biao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2016; EMBO Press; John Wiley and Sons Inc; Springer Nature
• Subjects: Alzheimer's disease; Animals; Brain research; Cell activation; Cell survival; CREB signaling; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Dephosphorylation; Diabetes; EMBO27; Experiments; Gene expression; Gliosis; Grants; Humans; Hypoxia; long non‐coding RNA; Metastasis; Mice; Microvasculature; Nervous system; Neurodegeneration; Neurodegenerative Diseases - pathology; Non-coding RNA; Phosphorylation; Protein Binding; Protein Processing, Post-Translational; Rats, Sprague-Dawley; reactive gliosis; Research Article; Retina; Retina - pathology; Retinal ganglion cells; retinal neurodegeneration; Ribonucleic acid; RNA; RNA, Long Noncoding - metabolism; Signal Transduction; Stress response; Variance analysis; Vascular system; reactive gliosis; CREB signaling; retinal neurodegeneration; long non‐coding RNA
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.15252/emmm.201505725

The nervous and vascular systems, although functionally different, share many common regulators of function maintenance. Long non‐coding RNAs (lncRNAs) are important players in many biological processes and human disorders. We previously identified a role of MALAT1 in microvascular dysfunction. However, its role in neurodegeneration is still unknown. Here, we used the eye as the model to investigate the role of MALAT1 in retinal neurodegeneration. We show that MALAT1 expression is significantly up‐regulated in the retinas, Müller cells, and primary retinal ganglion cells (RGCs) upon stress. MALAT1 knockdown reduces reactive gliosis, Müller cell activation, and RGC survival in vivo and in vitro . MALAT1‐CREB binding maintains CREB phosphorylation by inhibiting PP2A‐mediated dephosphorylation, which leads to continuous CREB signaling activation. Clinical and animal experimentation suggests that MALAT1 dysfunction is implicated in neurodegenerative processes and several human disorders. Collectively, this study reveals that MALAT1 might regulate the development of retinal neurodegeneration through CREB signaling. Synopsis Long non‐coding RNA MALAT1 knockdown decreases retinal reactive gliosis, Müller cell activation, and RGC survival via interactions with CREB signaling. MALAT1 expression is up‐regulated in retinas, Müller cells, and primary retinal ganglion cells (RGCs) under stress. MALAT1 knockdown decreases reactive gliosis, Müller cell activation, and RGC survival in vivo and in vitro . MALAT1 interacts with the CREB signaling pathway to regulate Müller cell and RGC function. MALAT1 dysregulation is implicated in several human neurological diseases. Graphical Abstract Long non‐coding RNA MALAT1 knockdown decreases retinal reactive gliosis, Müller cell activation, and RGC survival via interactions with CREB signaling.