Associate Professor Kumiko UI-TEI【Key Words】genome information, miRNA, siRNA, thermodynamics, epitranscriptome
In the cells, RNA is transcribed from genomic DNA, and is translated into protein with specific biological function. Such principle information flow from DNA→RNA→protein is called as the central dogma. For many years, RNA has been considered to act as the simple carrier of genetic information rom DNA to protein in the central dogma, but the recent researches focused on RNAs have revealed that RNAs are not simply an intermediary tool of information delivery; they instead serve many unique and important functions by themselves. RNAs which are not translated into proteins but function as RNAs are called non-coding RNAs (ncRNAs). We focused on the ncRNAs,especially on their genome-wide functions on the regulation of gene expression.
There are many different kinds of ncRNAs, from short double-stranded RNA with only about 20 bases to very long ones with tens of thousands,and they are involved in a wide variety of biological phenomena. In RNA silencing performed by microRNA and small interfering RNA (siRNA),both with approximately 20 bases each, the nucleotides approximately one-third of the full length of these small RNAs identify the target genes using the sequence complementarities, and suppress the expression of hundreds to thousands of messenger RNAs at once. Analyses related to such genome-wide regulations are important in ncRNA researches. We are performing such comprehensive studies by microarray or next generation sequencing analyses. We have also revealed that the thermodynamic stabilities in the microRNA duplex and microRNA-target RNA duplex can determine the extent of silencing efficacies (Fig.1). We are working with the goal of using these molecular biological and physicochemical properties to learn about mechanisms for controlling genome-wide genetic expression, and better understand important biological phenomena.
Fig1.Optomization of the factors to estimate possible miRNA-madiated gene silencing efficacy.
RNA binding proteins are important proteins related to a wide variety of biological functions, including RNA silencing, target gene identification, RNA editing, and even immune system response to RNA viruses. We are working to learn how these proteins function, by using large-scale sequencing or microarray analyses to perform comprehensive identification of their binding regions and their effects on gene expression.
RNA silencing via siRNA is called RNA interference (RNAi), and has become one of the most important tools in modern functional genomics. Since RNAi does not damage genomic DNAs, its clinical applications are expected. However not only a target gene with complete complementarity to siRNA but also non-target genes with partially complementary sequences are found to be suppressed in RNAi. By the mechanistic studies,we established targetspecific RNAi procedure for suppressing only a single target gene without affecting the expression of non-target genes (Fig. 2). Such method has been applied for various studies, such as functional genomics, protection against virus infection, or clinical applications. Furthermore, we would liketo hopeful apply such specific RNAi procedure for the analysis of gene network.
