Proper control of gene expression is essential for life. While substantial advances have been made in the discovery of DNA sequences and transcription factors that act combinatorially to regulate transcription, much less is known about later steps in the gene expression program. Nevertheless, it is now clear that substantial regulation of gene expression occurs post-transcriptionally, in pre-mRNA splicing, RNA transport, RNA localization, translation, and RNA decay, and in the coordination of RNAs by RNA binding proteins (RBPs). Further, recent findings of widespread transcription noncoding RNAs (ncRNA) and of the involvement of these RNAs in critical biological processes such as development and gene regulation suggest the existence of important classes of regulatory RNAs that we are just beginning to explore. The long term goal of this project is to enable structural characterization of RNAs on a genome-wide scale. First, we will apply a recently developed method to map secondary structures of most human RNAs. Second, we will examine how RNA secondary structures contribute to the functions of human long intergenic noncoding RNAs. Third, we will develop computational and experimental methods to further improve the precision and scope of genome-scale measurements of RNA structures. This integrated pipeline of new experimental and computational tools will enable investigators to identify and decode regulatory RNA elements in the genome with unprecedented speed and accuracy.

Public Health Relevance

The control of gene expression lies at the heart of understanding fundamental biological processes, such as cell growth, differentiation, and death. A deep and comprehensive understanding of the gene expression program would help to reveal the mechanisms of many human diseases exhibiting faulty gene expression, and allow their diagnosis and intervention with newfound precision.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project (R01)
Project #
Application #
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Pazin, Michael J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Medicine
United States
Zip Code
Tong, Jiyu; Cao, Guangchao; Zhang, Ting et al. (2018) m6A mRNA methylation sustains Treg suppressive functions. Cell Res 28:253-256
Chen, Lu; Roake, Caitlin M; Freund, Adam et al. (2018) An Activity Switch in Human Telomerase Based on RNA Conformation and Shaped by TCAB1. Cell 174:218-230.e13
Lu, Zhipeng; Chang, Howard Y (2018) The RNA Base-Pairing Problem and Base-Pairing Solutions. Cold Spring Harb Perspect Biol 10:
Li, Hua-Bing; Tong, Jiyu; Zhu, Shu et al. (2017) m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature 548:338-342
Simsek, Deniz; Tiu, Gerald C; Flynn, Ryan A et al. (2017) The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity. Cell 169:1051-1065.e18
Bailey, Alexis S; Batista, Pedro J; Gold, Rebecca S et al. (2017) The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline. Elife 6:
Lu, Zhipeng; Carter, Ava C; Chang, Howard Y (2017) Mechanistic insights in X-chromosome inactivation. Philos Trans R Soc Lond B Biol Sci 372:
Chen, Y Grace; Kim, Myoungjoo V; Chen, Xingqi et al. (2017) Sensing Self and Foreign Circular RNAs by Intron Identity. Mol Cell 67:228-238.e5
Lee, Byron; Flynn, Ryan A; Kadina, Anastasia et al. (2017) Comparison of SHAPE reagents for mapping RNA structures inside living cells. RNA 23:169-174
Schmitt, Adam M; Garcia, Julia T; Hung, Tiffany et al. (2016) An inducible long noncoding RNA amplifies DNA damage signaling. Nat Genet 48:1370-1376

Showing the most recent 10 out of 48 publications