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.