Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Post-transcriptional regulatory events are increasingly thought to play a critical role in the establishment of gene expression states. However, our current knowledge of these processes and the cellular context in which they function remains rather primitive. The proposed research combines state-of-the-art computational and experimental systems biology to reveal the vast landscape of RNA- regulatory interactions controlling the post-transcriptional fates of mammalian mRNAs.
Our aims are motivated by a set of exciting recent observations by our group that RNA-regulatory elements, and the factors that bind them, have substantial impact on transcriptome dynamics, steady-state abundance of proteins, and consequent cellular phenotypes such as growth. These recent observations have been enabled by the development of a new computational framework for discovering functional RNA regulatory elements from genome-wide molecular profile data on RNA behaviors and gene expression dynamics. In particular, we have made significance advances in identification of structural RNA elements and the interacting RNA binding proteins that regulate transcript stability. The phenomenal success of these efforts have motivated us to pursue a reverse-engineering strategy for decoding RNA-regulatory interactions and characterizing their biological contributions. In this interdisciplinary proposal we describe the details of our multi-faceted strategy which includes: (1) large-scale computational analysis of genomes and global RNA-behaviors (e.g. stability) to discover functional RNA regulatory elements, en masse;and (2) in vitro and in vivo experiments to determine the RNA binding proteins that interact with these elements. As such, the proposed work promises to fundamentally advance our understanding of gene regulation and enable a synthetic biology infrastructure for programming and manipulating mammalian gene expression states and cellular phenotypes.

Public Health Relevance

The proposed research is a systems biology approach at discovering how interactions between RNA and proteins affect the expression of genes. This knowledge is of fundamental importance to understanding processes that are affected in disease states.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Good, Peter J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Schools of Medicine
New York
United States
Zip Code
Alarcón, Claudio R; Goodarzi, Hani; Lee, Hyeseung et al. (2015) HNRNPA2B1 Is a Mediator of m(6)A-Dependent Nuclear RNA Processing Events. Cell 162:1299-308
Goodarzi, Hani; Zhang, Steven; Buss, Colin G et al. (2014) Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins. Nature 513:256-60
Oikonomou, Panos; Goodarzi, Hani; Tavazoie, Saeed (2014) Systematic identification of regulatory elements in conserved 3' UTRs of human transcripts. Cell Rep 7:281-92
Chiu, Isaac M; Morimoto, Emiko T A; Goodarzi, Hani et al. (2013) A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Rep 4:385-401
Goodarzi, Hani; Najafabadi, Hamed S; Oikonomou, Panos et al. (2012) Systematic discovery of structural elements governing stability of mammalian messenger RNAs. Nature 485:264-8
Birsoy, Kivanç; Berry, Ryan; Wang, Tim et al. (2011) Analysis of gene networks in white adipose tissue development reveals a role for ETS2 in adipogenesis. Development 138:4709-19
Lieber, Daniel S; Elemento, Olivier; Tavazoie, Saeed (2010) Large-scale discovery and characterization of protein regulatory motifs in eukaryotes. PLoS One 5:e14444
Goodarzi, Hani; Elemento, Olivier; Tavazoie, Saeed (2009) Revealing global regulatory perturbations across human cancers. Mol Cell 36:900-11
Lu, Xuemin; Li, Jennifer M; Elemento, Olivier et al. (2009) Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition. Development 136:2101-10
De Renzis, Stefano; Elemento, Olivier; Tavazoie, Saeed et al. (2007) Unmasking activation of the zygotic genome using chromosomal deletions in the Drosophila embryo. PLoS Biol 5:e117

Showing the most recent 10 out of 11 publications