Recognition of chromosomal DNA inside cells by locked nucleic acids.
Sequence-selective recognition of DNA inside cells by oligonucleotides would provide valuable insights into cellular processes and new leads for therapeutics. Recent work, however, has shown that noncoding RNA transcripts overlap chromosomal DNA. These RNAs provide alternate targets for oligonucleotides designed to bind promoter DNA, potentially overturning previous assumptions about mechanism. Here, we show that antigene locked nucleic acids (agLNAs) reduce RNA levels of targeted genes, block RNA polymerase and transcription factor association at gene promoters, and bind to chromosomal DNA. These data suggest that the mechanism of LNAs involves recognition of chromosomal DNA and that LNAs are bona fide antigene molecules.
Beane
Randall
R
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, Texas 75390-9041, USA.
Gabillet
Sylvie
S
Montaillier
Christophe
C
Arar
Khalil
K
Corey
David R
DR
D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D009841:Oligonucleotides; D011944:Receptors, Androgen; C477371:locked nucleic acid; D011374:Progesterone; D004247:DNA