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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Published on: August 9, 2019

Commandeering a biological pathway using aptamer-derived molecular adaptors.

Prabhat K Mallik¹, Kimi Nishikawa, Albert J T Millis

¹Department of Biological Sciences and Institute for RNA Science and Technology, University at Albany, State University of New York, Albany, NY 12222, USA.

Nucleic Acids Research

|January 8, 2010

Summary

Scientists engineered RNA aptamers to link target molecules to a utility molecule, hijacking the opsonization-phagocytosis pathway for targeted degradation. This creates a novel strategy for controlling biological processes and potential therapeutics.

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Area of Science:

Molecular Biology
Biotechnology
Immunology

Background:

Molecular proximity is crucial for biological responses.
Controlling biological processes can be achieved by creating specific protein connections.

Purpose of the Study:

To develop a method for imposing rational control over biological processes using engineered molecular adaptors.
To create a bi-functional aptamer linking a target molecule to a utility molecule for pathway activation.

Main Methods:

Designed composite RNA aptamers as molecular adaptors.
Created a bi-functional aptamer to bind green fluorescent protein (target) and opsonin C3b/iC3b (utility molecule).
Utilized the C3-based opsonization-phagocytosis pathway.

Main Results:

Successfully generated a bi-functional aptamer that links a surrogate extracellular target to the opsonization pathway.
Demonstrated selective transport of the extracellular target into the lysosome for degradation.
Established a novel strategy for controlling biological pathways.

Conclusions:

Engineered RNA aptamers can serve as molecular adaptors to control biological processes.
This strategy enables targeted degradation of extracellular molecules via the opsonization-phagocytosis pathway.
The approach holds potential for therapeutic applications targeting extracellular proteins or cancer cell surface markers.