A human lung cancer cell line (H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a 2-kilobase genomic segment of the K-ras protooncogene in antisense orientation. Translation of the mutated K-ras mRNA in H460a cells was specifically inhibited, whereas expression of H-ras and N-ras was unchanged. A 3-fold growth inhibition occurred in...

We describe the synthesis of 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides and demonstrate their utility as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. These 2'-O-modified compounds were designed to possess the binding affinity of an RNA molecule towards a complementary RNA target with an enhanced stability against nucleases...

We have tested the inhibitory potential of peptide nucleic acid (PNA) on in vitro reverse transcription of the HIV-1 gag gene. PNA was designed to target different regions of the HIV-1 gag gene and the effect on reverse transcription by HIV-1, MMLV and AMV reverse transcriptases (RTs) was investigated. We found that a bis-PNA (parallel antisense 10mer linked to antiparallel antisense 10mer) was...

Top1 inhibition by camptothecin (CPT) perturbs RNA polymerase II (Pol II) density at promoters and along transcribed genes suggesting an involvement of Top1 in Pol II pausing. Here, we demonstrate that Top1 inhibition favors Pol II escape from a promoter-proximal pausing site of the human HIF-1alpha gene in living cells. Interestingly, alternative splicing at exon 11 was markedly altered in nas...

We report the first example of antisense RNA regulation in a hyperthermophilic archaeon. In Sulfolobus solfataricus, the transposon-derived paralogous RNAs, RNA-257(1-4), show extended complementarity to the 3' UTR of the 1183 mRNA, encoding a putative phosphate transporter. Phosphate limitation results in decreased RNA-257(1) and increased 1183 mRNA levels. Correspondingly, the 1183 mRNA is fa...

ANRIL (Antisense Noncoding RNA in the INK4 Locus), a long non-coding encoded human chromosome 9p21 region, is critical factor for regulating gene expression by interacting with multiple proteins and miRNAs. It has been found to play important roles various cellular processes, including cell cycle control proliferation. Dysregulation of associated several diseases like cancers cardiovascular dis...

RNA plays a central role in the expression of all genes. Because any sequence within RNA can be recognized by complementary base pairing, synthetic oligonucleotides and oligonucleotide mimics offer a general strategy for controlling processes that affect disease. The two primary antisense approaches for regulating expression through recognition of cellular RNAs are single-stranded antisense oli...

A human lung cancer cell line (H460a) with a homozygous spontaneous k-rav mutation was transfected with a recombinant plasmiti that synthe sizes a 2-kilobase genomic segment of the K-ra.vprotooncogene in antisense orientation. Translation of the mutated k-rav inKNA in H460a cells was specifically inhibited, whereas expression of I l-rav and N-ras was unchanged. A 3-fold growth inhibition occurr...