The Mechanism Of The Regulating Expression Of Host Gene Trio By Intron Long Non-coding RNA CR45811

Regulation of gene expression is an essential regulatory mechanism for organisms to maintain growth,proliferation,development and differentiation and to adapt to the external environment.Mastering the concepts of time and space of gene expression regulation can better explore the laws related to plant and animal growth and development.The Human Genome Project discovered in 2011 that most of the human genome is non-protein coding sequences.At first,these non-coding transcripts were considered as"noise"of transcription.With the continuous development ofRNA sequencing technology,people have a new understanding of non-codingRNA（ncRNA）.More and more evidence show that non-codingRNA has important biological significance in cell life activities.Long non-codingRNA（LncRNA）often refers to non-coding transcripts with a length of more than 200 nt,and lncRNAs have extensive regulatory effects on gene expression.According to their different regulatory mechanisms,they usually serve four functions:signal,bait,guide and support.Signal molecules means the state of chromatin can be inferred according to their expression.Bait molecules means recruit otherRNA-binding proteins to jointly regulate target genes.Guiding molecules means guide some protein complexes to reach the designated regulatory sites and regulate gene expression through cis or trans action;Scaffold molecules means provide an assembly platform for members of biological signal transmission or intermolecular interaction.Guanylate exchange factor（GEF）is a small GTPase protein of the Rho family that catalyzes the conversion between GTP and GDP.The trio gene is a member of the GEF family.The trio gene is highly conserved in mammals,drosophila and nematodes.Existing studies have shown that trio genes are closely related to neurological development,and their abnormal functions often lead to a variety of neurological diseases,but the specific regulatory mechanism remains to be explored.Previous data of our research group showed that the expression of CR45811 in p53mutant Drosophila was significantly reduced.In order to further explore the function of CR45811,we established CR45811 knockout Drosophila melanogaster in the early stage and found that CR45811 ^KODrosophila melanogaster has an obvious wing defect phenotype,which is similar to some homozygous Drosophila melanogaster with trio gene mutations,so it is inferred that the knockout of CR45811 may affect the expression of the trio gene.Based on the conclusions of previous experiments,it was confirmed that CR45811 has two transcripts and multiple variants,and miR-33targeting trio was detected by dual-luciferase reporter system detection,and the experimental results were confirmed at the animal level.In addition,it was also found that the expression level of CR45811 and miR-33 may be inversely correlated,which preliminarily confirmed the mechanism of CR45811 regulating trio expression of host genes through miR-33.