ABSTRACT
Nearly 97% of the human genome is noncoding DNA, which varies from one species to another, and changes in these sequences frequently manifest clinical and circumstantial malfunction. Numerous noncoding DNA regions have been recently found to encode microRNA (miRNA) genes, which are responsible for RNA-mediated gene silencing through RNA interference (RNAi)-like pathways. miRNAs, 17 to 25 nucleotide single-stranded RNAs that are capable of regulating targeted gene transcripts with high complementarity, are useful for the development of new therapies against cancer polymorphism and viral mutation. This flexible characteristic is different from double-stranded siRNAs (small interfering RNAs), which require completely matched complementarity for targeted gene silencing. miRNAs were first discovered in Caenorhabditis elegans as native small RNAs that modulate a wide range of genetic regulatory pathways during embryonic development. Varieties of
Overview ................................................................................................................ 275 15.1 Introduction .................................................................................................. 276 15.2 Definition and Biogenesis of Intronic miRNA ............................................. 278
15.2.1 Intronic miRNA and Microsatellite-Associated Diseases ...............280 15.2.2 Synthetic Intronic miRNA................................................................ 282
15.3 Transgene-Like Gene Silencing in Mice ......................................................285 15.3.1 First miRNA-Mediated Transgenic Animal Model-FXS Zebra
Fish....................................................................................................286 15.4 Generation of Intronic miRNA-Mediated FXS Zebra Fish Lines ...............288 15.5 Similar miRNA-Induced Abnormalities in Human and Fish FXS .............. 293 15.6 Conclusions ................................................................................................... 295 Acknowledgments .................................................................................................. 295 References ..............................................................................................................296
