A novel RNA splicing-mediated gene silencing mechanism potential for genome evolution.
Over 90% of the human genome consists of non-protein-coding regions. Introns constitute most of the non-coding regions located in precursor messenger RNAs (pre-mRNAs). During pre-mRNA maturation, the introns are excised out of mRNA and thought to be completely digested prior to translation. If the introns were merely metabolic "leavings," why would the genome hold such a large amount of extraneous genetic materials? Here we show a novel posttranscriptional gene silencing system identified within mammalian introns. By packaging human spliceosome-recognition sites along with an exonic insert into an artificial intron, we observed that the splicing and processing of such an exon-containing intron in either sense or antisense conformation produced equivalent gene silencing effects, while a palindromic hairpin insert containing both sense and antisense strands resulted in synergistic effects. These findings may explain how cells respond to the presence of transgenic introns that are homologous to pre-existing exons during genomic evolution.
Lin
Shi-Lung
SL
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. lins@usc.edu
Chang
Donald
D
Wu
Da-Yu
DY
Ying
Shao-Yao
SY
D000818:Animals; D019143:Evolution, Molecular; D005091:Exons; D020868:Gene Silencing; D005822:Genetic Vectors; D016678:Genome; D049452:Green Fluorescent Proteins; D006801:Humans; D007438:Introns; D008164:Luminescent Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017381:Spliceosomes / Q000378:metabolism
D008164:Luminescent Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins