小分子RNA与心血管疾病课件.pptVIP

MicroRNAs in Vascular Disease the beginning of a new tale Chunxiang Zhang M.D., Ph.D. University of Medicine and Dentistry of New Jersey MiroRNAs MicroRNAs (miRNAs) are a novel class of endogenous, small, noncoding RNAs that regulate gene expression. Mature miRNAs are 18- to 24-nucleotide(nt)-long. They negatively regulate protein expression of their target mRNAs by either translation inhibition or degradation. As a group, miRNAs are estimated to regulate at least 30% of the human genes. Pathway of Genetic Information Flow and RNA “revolution” 1.The standard pathway of information flow in a cell. 2. DNA Transcription and RNA products 3. The first RNA revolution. Discovery of miRNA - The second RNA “revolution” Discovery of RNAi. With the help of RNAi technology, two regulatory noncoding RNAs were found, interfering RNAs (siRNA) and endogenous miRNAs. The recent discoveries of RNAi and miRNA represent the second RNA revolution (Kong et al. Genomics Proteomics Bioinformatics. 2005;3: 62-72). miRNAs and siRNAs siRNAs and miRNAs have similar mechanism for gene expression regulation. However, they are different from each other. The chief difference lies in their origins: SiRNAs are produced from long double-stranded (bimolecular) RNAs or long hairpins, often of exogenous origin. In contrast, miRNAs are endogenous. They are encoded within the genome and come from endogenous short hairpin precursor. Therefore, miRNAs are more important because they are endogenous regulators for gene expression. Biogenesis of miRNAs and their molecular mechanism for gene regulation Biological functions of miRNAs Although only a small number from hundreds of identified miRNAs have been characterized, a growing body of exciting evidence suggests that miRNAs are important regulators for cell growth, differentiation, and apoptosis. Therefore, miRNAs could be the important endogenous regulators in normal development, physiology, as well as in