Related Experiment Video
Updated: Aug 13, 2026

Isolation of Cognate RNA-protein Complexes from Cells Using Oligonucleotide-directed Elution
Published on: January 16, 2017
Mechanism of oligonucleotide uptake by cells: involvement of specific receptors?
L A Yakubov1, E A Deeva, V F Zarytova
1Institute of Bioorganic Chemistry, Siberian Division of the Academy of Sciences of U.S.S.R., Novosibirsk.
Abstract:
We have investigated the interaction of oligonucleotides and their alkylating derivatives with mammalian cells. In experiments with L929 mouse fibroblast and Krebs 2 ascites carcinoma cells, it was found that cellular uptake of oligodeoxynucleotide derivatives is achieved by an endocytosis mechanism. Uptake is considerably more efficient at low oligomer concentration (less than 1 microM), because at this concentration a significant percentage of the total oligomer pool is absorbed on the cell surface and internalized by a more efficient absorptive endocytosis process. Two modified proteins were detected in mouse fibroblasts that were treated with the alkylating oligonucleotide derivatives. The binding of the oligomers to the proteins is inhibited by other oligodeoxynucleotides, single- and double-stranded DNA, and RNA. The polyanions heparin and chondroitin sulfates A and B do not inhibit binding. These observations suggest the involvement of specific receptor proteins in binding of oligomers to mammalian cells.
Insights
Oligonucleotide derivatives enter mammalian cells via endocytosis, with higher efficiency at lower concentrations. Specific cell surface proteins likely mediate this uptake, suggesting targeted delivery potential.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Oligonucleotides and their derivatives are increasingly explored for therapeutic applications.
- Understanding their cellular uptake mechanisms is crucial for effective drug delivery.
- Mammalian cell interactions with these molecules require detailed investigation.
Purpose of the Study:
- To investigate the cellular uptake mechanisms of oligonucleotides and their alkylating derivatives in mammalian cells.
- To identify the factors influencing the efficiency of oligodeoxynucleotide uptake.
- To explore the potential involvement of specific cellular components in oligomer binding.
Main Methods:
- Experiments were conducted using L929 mouse fibroblast and Krebs 2 ascites carcinoma cells.
- Cellular uptake was analyzed using varying concentrations of oligodeoxynucleotide derivatives.
- Protein binding interactions were assessed by testing inhibition with various nucleic acids and polyanions.
Main Results:
- Cellular uptake of oligodeoxynucleotide derivatives occurs via endocytosis.
- Uptake efficiency is significantly higher at concentrations below 1 microM due to absorptive endocytosis.
- Two modified proteins were detected in treated mouse fibroblasts, indicating specific interactions.
- Binding to these proteins was inhibited by other nucleic acids but not by heparin or chondroitin sulfates.
Conclusions:
- Oligodeoxynucleotide derivative uptake is mediated by an endocytosis mechanism, enhanced at low concentrations.
- Specific receptor proteins on the cell surface are likely involved in the binding and internalization of oligomers.
- These findings suggest potential for receptor-mediated drug delivery strategies using oligonucleotide derivatives.
Related Concept Videos
Receptor-mediated Endocytosis
Receptor-mediated Endocytosis
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Nuclear Protein Sorting
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Nuclear Localization Signals and Import
Regulation of Nuclear Protein Sorting
Receptor-Mediated Endocytosis
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...

