​​Genome-wide Probing of RNA Structures


​Understanding structure is key to knowing how macromolecules work.  Much work has been done in the past decades to solve the structures of proteins, in order to understand how they function in the cells.  Recently, RNA has emerged as another class of important cellular machines, whose function is strongly dictated by its structure.  Unlike proteins, RNAs are notoriously difficult to crystallize, and efforts to solve RNA structures are frequently restricted to short RNAs that are protein bound. While other biochemical assays have been developed to probe RNA structures, these assays are typically tedious and time consuming.  As a result, structure information for the majority of the RNA transcripts is absent, limiting our ability to understand RNA biology.  To solve this problem of a lack of RNA structure data, we developed a new technology, named Parallel Analysis of RNA Structures (PARS), to enable the determination of thousands of RNA structures at the same time. PARS has been applied to study the transcriptomes of yeast and humans, as well as to study the impact of temperature and mutations on RNA structure.


​Yue Wan et al, Landscape and variation of RNA secondary structure across the human transcriptome. Nature 2014 Jan 30;505(7485):706-9.  


Yue Wan et al, Genome-wide measurement of RNA folding energies. Molecular Cell 48(2):169-81. 2012


Yue Wan et al. (2011) Understanding the transcriptome through RNA structure. Nature Reviews Genetics12(9):641-55.


Michael Kertesz*, Yue Wan* et al (2010) Genome-wide Measurement of RNA Secondary Structure in Yeast.  Nature 467(7311):103-7.   * these authors contributed equally. 




  



Genome-wide Mapping of RNA-RNA interactions.


The ability of RNA to pair within itself and with others is crucial for its function in vivo.  However, the prevalence of long range intramolecular and intermolecular RNA interactions is still unknown.  In this study, we utilized in vivo crosslinking followed by proximity ligation and deep sequencing to identify pair-wise intramolecular and intermolecular RNA-RNA interactions in eukaryotes.  Our study reveals extensive intra and intermolecular interaction networks that can be remodeled under different cellular states.


Ashley Aw et al, In vivo mapping of eukaryotic RNA interactomes reveals principles of higher-order organization and regulation. Molecular Cell . 2016 May 19;62(4):603-17



RNA folds into complex secondary and tertiary structures that is key to its function.  However due to the tedious nature of RNA structure probing, RNA structure information for most of the transcripts in the cell is missing.  We aim to develop and utilize new genomics tools to study RNA structures in a high throughput manner, in order to understand how RNAs function in pathogens and mammalian systems.

Wan Lab of RNA Structure Genomics

Genome Institute of Singapore