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Recognition of chromosomal DNA inside cells by locked nucleic acids.

ABSTRACT: 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.

SUBMITTER: Beane R

PROVIDER: S-EPMC2627484 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Recognition of chromosomal DNA inside cells by locked nucleic acids.

Beane Randall R Gabillet Sylvie S Montaillier Christophe C Arar Khalil K Corey David R DR

Biochemistry 20081201 50

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 R ...[more]

PMID: 19053275

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