Methods for Discovering RNA Structural Regulatory Elements and Affecting Their In Vivo Function

Web Published:
5/22/2012
Description:

TEISER (Tool for Eliciting Informative structural elements in RNA) - A Novel Computational Algorithm for Systemically Discovering RNA Structural Regulatory Elements in Research and Drug Discovery

Princeton Docket # 12-2796-A

Researchers in the Molecular Biology Department, Princeton University, have developed TEISER (Tool for Eliciting Informative structural elements in RNA), a novel computer algorithm for systemic discovery of structural elements governing stability of mammalian mRNAs.  The algorithm is based on context-free grammars and mutual information that systematically explores the immense space of small structural elements and reveals motifs that are significantly informative of genome-wide measurements of RNA behavior.  TEISER can be applied to discover the specific recognition sequence/structure of any RNA binding protein.  These include discovering post-transcriptional and translational regulatory elements involved in any regulatory process in the cell, such as elements modulating mRNA stability, mRNA splicing, mRNA localization and mRNA translation.

TEISER can be used to discover RNA regulatory elements involved in a wide range of applications, including molecular characterization or regulatory perturbations in disease states including cancer.  As an example, Princeton researchers have discovered eight highly significant elements (sRSM1-8, structural RNA stability motifs) with substantial structural information, the strongest of which (sRSM1) has been demonstrated to play a major role in global mRNA regulation. 

Applications        

For genome-wide discovery of RNA structural regulatory elements

Advantages         

·        Novel

·        Deep and systemic

·        Highly sensitive

Intellectual Property and Commercialization Strategy

A provisional application has been filed. 

For further development and commercialization, Princeton University is pursuing a non-exclusive licensing strategy for the computer algorithm.

RNA Decoy Titration Knock-Down Technology - A Novel Method for Specifically Regulating the Functions of RNA-Binding Proteins

Princeton Docket # 12-2796-B

Princeton researchers in the Molecular Biology Department, Princeton University, have developed a RNA-decoy titration knock-down technology, which allows targeting of RNA-binding proteins by introducing copies of its recognition sequence into the cell.

The method consists of delivering instances of the specific RNA structural elements (called the decoy), in single copy or multiple copies, into a cell.  A range of delivery methods could be employed, including but not limited to RNA transfection and viral transduction/phage infection.  In cases where the introduction of external RNA may have deleterious consequences (as in mammalian cells), the RNAs can be modified by the addition of 5' CAP and 3' poly-A tail.  Once inside the cell, these decoys will compete with endogenous targets of the RNA-binding protein for binding and therefore, in effect, displace the RNA-binding protein from its native sites throughout the genome. This decoy-titration process has the effective consequence of reducing the function of the specific RNA-binding protein that recognizes the decoy. The efficacy of this RNA-decoy titration knock-down effect can be monitored by assaying for the relevant RNA behavior of the native targets of the RNA-binding protein. For example, if the function of the RNA-binding protein is to stabilize mRNAs, the RNA-decoy titration knock-down would be expected to decrease the stability of the targets.

This RNA-decoy titration knock-down technology is a versatile approach for modulating the function of RNA-binding proteins and is complementary to siRNA/shRNA knockdown.

Applications        

For targeting and interfering with the function of an RNA-binding protein

·        As a therapeutic

·        In industrial settings

Advantages         

·        Versatile

·        Specific

·        Complementary to siRNA/shRNA knockdown

Intellectual Property and Commercialization Strategy

A provisional application has been filed. 

Princeton is interested in identifying partners for further development and commercialization of this technology

A Novel Method for Modulating Cell Proliferation Rate for
Clinical, Industrial and Research Applications

Princeton Docket # 12-2796-C

 

Through biochemistry, mass spectrometry and in vivo binding studies, Princeton researchers identified human HNRPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1) as the key regulator that binds sRSM1 and stabilizes a large number of its target genes.  Modulation of HNRPA2B1 resulted in  a significant change in proliferation rate in human cancer cells lines.  Thus, manipulation of this protein can be applied to alter cell proliferation in any clinical and/or industrial settings.

Advantage 

Novel mechanism

Applications        

Modulation of cellular proliferation by interfering with HNRPA2B1 for

·        Clinical applications including treating

o   Cancer

o   Non-neoplastic endothelial tissue diseases (arteriosclerosis, proliferative retinal disorders, hemangioma, cheloids, fibrosis, etc.)

·        Industrial applications including

o   Synthetic biology

o   Biotechnological engineering

Intellectual Property and Commercialization Strategy

A provisional application has been filed. 

Princeton is interested in identifying partners for further development and commercialization of this technology

Publication

Goodarzi H, Najafabadi HS, Oikonomou P, Greco TM, Fish L, Salavati R, Cristea IM, Tavazoie S. Systematic discovery of structural elements governing stability of mammalian messenger RNAs.  Nature. (2012) doi: 10.1038/nature11013.

Inventors

Saeed Tavazoie is Professor of Biochemistry and Molecular Biophysics in Columbia University.  The focus of his research is to understand the organizing principles that underlie the evolution and function of molecular networks. Prof. Tazazoie¿s honors include a CAREER Award from the National Science Foundation and NIH Director¿s Pioneer Award.

Hani Goodarzi is a postdoctoral fellow in Prof. Tavazoie¿s lab at Columbia University.

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
tzodikov@Princeton.EDU
Inventors:
Saeed Tavazoie
Hani Goodarzi
Keywords:
bioinformatics
life science research tools