LncRNA SNHG20 Deteriorates Cognitive Function By Inhibiting C-Fos Transcription

Higher organisms learn and adapt to the changes from the environment.They evolve by transforming short-term stimuli into long-term changes of structure and fuction in brains.This conversion process is related to many changes such as receptor transport,synthesis of new genes,translation of local mRNA,and protein turnover.It is specifically manifested that the specific synapses release neurotransmitters,and then the neurotransmitters bind to the corresponding receptors at the post-synaptic neurons,that induce a series of biochemical signaling reactions.The most prominent of these is that calcium levels will increase rapidly and briefly during the post-synaptic specialization.Increased local calcium concentration can cause short-term or long-term specific changes in the synapse,including the glutamate receptor subunits of cell membrance inserting or removing,and the fuction changes or translation and degradation of synaptic proteins.Other than these synaptic changes,after calcium flow into the cells,neurons will also trigger a series of signal events.The signals will transmit to the nucleus and lead to expression of related genes.The expression of many genes has been confirmed to be regulated by neuronal activity,and remarkably,c-Fos has been repeatedly mentioned as a marker gene for neuronal activation,but the reason for its rapid change is not clear.In this study,we found that lncRNA SNHG20 can inhibit the transcription of c-Fos and affect learning and memory.By analyzing the sequencing data of KCl-activated neurons,it was found that SNHG20 was significantly down-regulated after KCl stimulation,and then verified by real-time fluorescence quantitative PCR(RT-qPCR).After overexpression of SNHG20 in neurons by a lentivirus-mediated approach,c-Fos mRNA and protein levels were suppressed during neuronal activation.Using 4-Thiouridine(4sU)to label nascent RNA,it was found that overexpression of SNHG20 inhibited the synthesis of c-Fos mRNA.It was further found that SNHG20 participated in the level regulation of downstream target genes in its pathway,especially Annexin A2(ANXA2),by regulating the level of c-Fos,which in turn affects cognitive function.The experiment of overexpression of SNHG20 in the hippocampus in vivo showed that mice overexpressing SNHG20 showed obvious learning and memory dysfunction.