Role And Underlying Mechanisms Of LncRNA AK013786 In Social Hierarchy

Background: Social hierarchy is a ubiquitous principle of social organization and helps groups and organizations survive and prosper.Social hierarchy has a profound impact on survival,health,and show characteristic hierarchy-related disease of human and animals.Although social domain and its effective discovered by many years,little is known about the underlying of relative mechanism.Long noncoding RNAs(lnc RNAs)are a large and diverse class of RNA transcripts longer than 200 nucleotides that have little or no protein-coding capacity,which have a 5’ cap structure.Lnc RNAs can regulate gene expression through a diversity of mechanisms.While there is no report about the function of lnc RNA in social hierarchy.Some studies have indicated that the m PFC may play a specific role in social dominant regulation,the relative evidence come from the methods of surgical lesion,f MRI and electrophysiology.However the molecular mechanism is still unclear.Objective: To study the role and mechanisms of lnc RNA in the m PFC that regulate social domainMethods: 3-month C57 mice,AK013786 knockout mice,293 T cell and primary cell were used for this research.Dominant mice and subordinate ones were identified by three classical behavior test.Arraystar lnc RNA microarray and bioinformatical analysis performed by selective expression difference ones.To verify the changed lnc RNA in social hierarchy analyzed by q PCR.Bioinformatic approaches and construct recombination plasmid.to determine the likelihood of protein-coding potential in lnc RNA.Subcellular localization of lnc RNA expression by fluorescence in situ hybridization.Using CRISPR/Cas9 mediated genome editing technology generating gene knockout mice.To test basic characteristic by weighing,rotarod test,open field and spontaneous alternation T-maze.Isolation dominant mice and subordinate ones through tube test.Miniature excitatory synaptic currents(m EPSCs)measured by whole-cell to investigated potential differences in the synaptic strength.Lnc RNA targeted molecular detected by PCR and western blotting.Overexpression lnc RNA and its target molecular by injecting their relative adeno-associated virus by stereotactic instrument and test their effect by behavior and electrophysiology.Results: we identified dominant mice and subordinate ones by behavior test and isolated respective brain tissues of m PFC to perform lnc RNA microarray analysis.We picked out 40 lnc RNAs which change significantly followed quantitative polymerase chain reaction(q PCR)assay.AK013786 displayed the most dramatically alteration in the dominant mice.AK013786 has no coding capacity and localizes to nuclear and cytoplasm regions.We generated AK013786 knockout mice(AK-KO)by CRISPR/Cas9 technology.AK-KO mice didn’t display any developmental deficits and locomotors abnormalities and performed similar with domain mice in open filed and T-maze.AK-KO mice displayed the higher rank in domain test and larger amplitudes in m EPSCs than the wild type littermates,while injection AK013786 virus changed those advantage.AK013786 regulate the expression of syn2 a and syn2 b.Syn2b viral manipulations in m PFC of C57 and AK-KO mice showed down-regulate rank in hierarchy.The synaptic strength induced by AK013786/Syn2 b may be dependent by AMPAR trafficking to synapses.Conclusion: This study confirms that lnc RNAs expression difference between dominant mice and subordinate ones.Up or down regulate AK013786 can bidirectional Control of Social Hierarchy.AK013786 may governs social hierarchy by changing syn2 b expression to regulate postsynaptic strength.