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Biomedical subjects

O V Matveeva

Publications and source records attributed to O V Matveeva.

7 recordsLinked to original sources

Identification of sequence motifs in oligonucleotides whose presence is correlated with antisense activity.

Design of antisense oligonucleotides targeting any mRNA can be much more efficient when several activity-enhancing motifs are included and activity-decreasing motifs are avoided. This conclusion was made after statistical analysis of data collected from >1000 experiments with phosphorothioate-modified oligonucleotides. Highly significant positive correlation between the presence of motifs CCAC, TCCC, ACTC, GCCA and CTCT in the oligonucleotide and its antisense efficiency was demonstrated. In addition, negative correlation was revealed for the motifs GGGG, ACTG, AAA and TAA. It was found that the likelihood of activity of an oligonucleotide against a desired mRNA target is sequence motif content dependent.

Base Composition↗

ODNBase--a web database for antisense oligonucleotide effectiveness studies. Oligodeoxynucleotides.

SUMMARY: ODNBase is a database of antisense oligodeoxynucleotides targeted to mammalian mRNAs that were reported in the literature. It includes the oligo sequences tested, the measured effectiveness, the RNA that was targeted, the type of measurement assay used, the oligo concentration applied, and the reference for each oligo. It provides a searchable interface by motif content, activity level, applied concentration and RNA name. Oligo lists matching search criteria can be downloaded in a spreadsheet compatible format.

Animals↗

Intermolecular mRNA-rRNA hybridization and the distribution of potential interaction regions in murine 18S rRNA.

Intermolecular hybridization experiments show that murine 18S rRNA and 28S rRNA are capable of forming stable hybrid structures with mRNA from genes p53, c-myc and c-mos from the same species. Both 5'-uncoding and coding oncogene p53 mRNA regions contain fragments interacting with rRNA. Computer analysis revealed 18S rRNA fragments complementary to oligonucleotides frequently met in mRNA, which are potential hybridization regions (clinger-fragments). The distribution of clinger-fragments along 18S rRNA sequence is universal at least for one hundred murine mRNA sequences analyzed. Maximal frequencies of oligonucleotides complementary to 18S rRNA clinger-fragments are reliably (2-3 times) higher for mRNA than for intron sequences and randomly generated sequences. The results obtained suggest a possible role of clinger-fragments in translation processes as universal regions of mRNA binding.

Animals↗

[Interaction of mRNA of the p53 protein gene with ribosomal RNA].

By blot hybridization we found that DNA fragments of eukaryotic 18 and 28S rRNAs bind specifically with mRNA. In these experiments the in vitro transcribed mRNA of mouse gene p53 was used. In addition we found that both 18 and 28S rRNAs were able to form intermolecular complexes with mRNAs of several genes 18S rRNA-mRNA; 28S rRNA-mRNA, but fail to bind the antisense RNAs of the same genes. The experimental data allow to suppose that 18S and 28S rRNAs carry several fragments that are complementary to some fragments in the mRNA sequences.

Animals↗

[A model of multiple contacts, describing the interaction of rRNA sites with mRNA].

A model describing the interaction of a short oligonucleotide with long polynucleotide matrix has been developed. The model allows to calculate possibilities of oligonucleotide binding with different matrix sites on the basis of thermodynamic parameters of duplex formation. The model has been used for description of messenger RNA interaction with "clinger-fragment" sites on ribosomal RNA, which are potential sites of hybridization with mRNA. A possibility of rRNA interaction with mRNA by means of multiple duplex formation between "clinger-fragments" and numerous complementary short mRNA sites is discussed.

Base Sequence↗