Micro-RNA-like effects of complete intronic sequences.
MicroRNAs (miRNAs) have been suggested as suppressors of numerous target genes in human cells. In this report, we present gene chip array data indicating that in the absence of miRNA sequences, complete human introns are similarly capable of coordinating expression of large numbers of gene products at spatially diverse sites within the genome. The expression of selected intronic sequences (6a, 14b and 23) derived from the cystic fibrosis transmembrane conductance regulator (CFTR) gene caused extensive and specific transcriptional changes in epithelial cells (HeLa) that do not normally express this gene product. Each intron initiated a distinctive pattern of gene transcription. Affected genes such as FOXF1, sucrase-isomaltase, collagen, interferon, complement and thrombospondin 1 have previously been linked to CFTR function or are known to contribute to the related processes of epithelial differentiation and repair. A possible regulatory function of this nature has not been demonstrated previously for non-coding sequences within eukaryotic DNA. The results are consistent with the observation that splicesomal introns are found only in eukaryotic organisms and that the number of introns increases with phylogenetic complexity.
Hill
Aubrey E
AE
Pittman General Clinical Research Center, University of Alabama, Birmingham, Alabama 35294, USA.
Hong
Jeong S
JS
Wen
Hui
H
Teng
LiHong
L
McPherson
David T
DT
McPherson
Sylvia A
SA
Levasseur
Dana N
DN
Sorscher
Eric J
EJ
D002454:Cell Differentiation; D002460:Cell Line; D019295:Computational Biology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D005091:Exons; D005786:Gene Expression Regulation; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D016086:Lentivirus / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D017381:Spliceosomes / Q000378:metabolism; D014158:Transcription, Genetic; D014945:Wound Healing
C505032:CFTR protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA