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.
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.
|Buenrostro, Jason D; Araya, Carlos L; Chircus, Lauren M et al. (2014) Quantitative analysis of RNA-protein interactions on a massively parallel array reveals biophysical and evolutionary landscapes. Nat Biotechnol 32:562-8|
|Wan, Yue; Qu, Kun; Zhang, Qiangfeng Cliff et al. (2014) Landscape and variation of RNA secondary structure across the human transcriptome. Nature 505:706-9|
|Spitale, Robert C; Flynn, Ryan A; Torre, Eduardo A et al. (2014) RNA structural analysis by evolving SHAPE chemistry. Wiley Interdiscip Rev RNA 5:867-81|
|Spitale, Robert C; Crisalli, Pete; Flynn, Ryan A et al. (2013) RNA SHAPE analysis in living cells. Nat Chem Biol 9:18-20|
|Ouyang, Zhengqing; Snyder, Michael P; Chang, Howard Y (2013) SeqFold: genome-scale reconstruction of RNA secondary structure integrating high-throughput sequencing data. Genome Res 23:377-87|
|Batista, Pedro J; Chang, Howard Y (2013) Cytotopic localization by long noncoding RNAs. Curr Opin Cell Biol 25:195-9|
|Dvir, Shlomi; Velten, Lars; Sharon, Eilon et al. (2013) Deciphering the rules by which 5'-UTR sequences affect protein expression in yeast. Proc Natl Acad Sci U S A 110:E2792-801|
|Kretz, Markus; Siprashvili, Zurab; Chu, Ci et al. (2013) Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493:231-5|
|Gomez, J Antonio; Wapinski, Orly L; Yang, Yul W et al. (2013) The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-ýý locus. Cell 152:743-54|
|Ilik, Ibrahim Avsar; Quinn, Jeffrey J; Georgiev, Plamen et al. (2013) Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila. Mol Cell 51:156-73|
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