RNA Regulation Units for Alternative Polyadenylation Control
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Solution Overview
Problem
Current methods for regulating alternative polyadenylation (APA) lack a comprehensive list of RNA binding proteins (RBPs) with known binding-locale specific effects, limiting the ability to modulate APA site usage effectively.
Innovation Solution
Assembling an RNA regulation unit comprising an RNA binding protein (RBP) and a gene-targeting agent, which binds proximal to a poly(A) signal and/or site, to regulate APA, stability, localization, and translation of target RNA in cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If low throughput methods coupling RBP knockdown with experimental observation are used, then specific RBP effects on poly(A) site selection can be observed, but comprehensive identification of RBPs with binding-locale specific effects cannot be achieved
Solution Approach 1:
The patent combines multiple functions into a single RNA regulation unit: the gene-targeting agent provides sequence-specific binding to the target RNA, the RBP binds proximal to the poly(A) signal to regulate APA, and the system enables both specific observation and comprehensive identification of RBP effects simultaneously
Solution Approach 2:
The RNA regulation unit is designed as a universal platform that can be applied to regulate APA of any target RNA by simply changing the gene-targeting agent sequence, enabling comprehensive identification of RBPs across multiple targets without developing new methods for each target
2Adaptability or versatility
If RNA binding proteins are used to regulate alternative polyadenylation, then poly(A) site usage can be modulated, but a comprehensive list of RBPs with known binding-locale specific effects is not available
Solution Approach 1:
The patent performs preliminary identification and characterization of RBPs with binding-locale specific effects on APA, creating a knowledge base that can be used for future applications. The system pre-establishes which RBPs work at which locations to inform subsequent experimental design
Solution Approach 2:
The system incorporates detection of changes in target RNA translation and stability as feedback to verify successful APA regulation. This feedback mechanism allows identification of RBPs that produce the desired effects, building a comprehensive list of functional RBPs
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The RNA regulation unit effectively regulates APA, increasing stability, preventing degradation, modifying localization, and enhancing protein synthesis of target RNA by detecting changes in translation.
Implementation Method 1
an RNA binding protein (RBP), and a gene-targeting agent, wherein the RNA binding protein binds proximal to a poly(A) signal
Data Source
AI summary
Provided herein are methods of regulating alternative polyadenylation (APA) of a target RNA in a cell, increasing stability of a target RNA in a cell, preventing degradation of a target RNA in a cell, preventing degradation of a target RNA in a cell, modifying localization of a target RNA in a cell, or increasing synthesis of a protein encoded by a target RNA in a cell, by administering to the cell an RNA regulation unit, wherein the RNA regulation unit comprises an RNA binding protein (RBP) and a gene-targeting agent, wherein the RNA binding protein binds proximal to a poly(A) signal and/or site.