Nuclear targeting of antisense oligonucleotides: modification of PRE-mRNA splicing or inhibition of polyadenylation?
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to V Tomasi.
Explore the source record for details and available documents.
Recent studies suggest that antisense phosphorothioate oligonucleotides (APO) are useful tools not only to impair gene expression, but also to modify the splicing of pre-mRNA, as the classical view that they act by suppressing the translation of mature mRNA has been challenged by several examples showing their nuclear site of action. In this work we show that an APO directed against cytosolic phospholipase A2 (cPLA2) mRNA localises in the nucleus and interacts with a specific nuclear protein.
Nuclear accumulation of ODNs has been associated with their binding to a series of nuclear proteins. These interactions could be responsible for the sequence-independent effects of ODNs as well as for their sequence-specific interactions and their intracellular distribution. Investigation of interaction of ODNs with these proteins may shed light on the mechanisms of cellular uptake and nuclear accumulation of oligonucleotides.
This paper reviews the evidence pointing to a role of prostaglandins and cyclic AMP in the regulation of surveillance processes against transformed cells carried out by activated monocytes macrophages and natural killer (NK) cells. Specific topics of discussion include: (a) the regulation of monocyte/macrophage system and NK cells by prostaglandins and cyclic AMP; and (b) the possible immunomodulatory role of thromboxanes generated by activated monocytes and macrophages. Also the role of cyclic AMP dependent and independent protein kinases as well as their link with oncogenes is briefly reviewed.
Explore the source record for details and available documents.