WAN Yue

RESEARCH

Research Summary

My research aims to identify functional RNA elements in transcriptomes through genome-wide detection of RNA structures. RNA play an important role in regulating cellular gene expression. Its ability to fold into complex secondary and tertiary structures is fundamental to its function in the cell. In almost every step of its life cycle, RNA structure has been found to influence diverse processes including transcription, translation mRNA transcript and decay. Alterations in RNA structure have been implicated in several diseases. Despite the importance of RNA structure, structural information for most cellular RNAs, such as mRNAs, is lacking due to the low throughput nature of RNA structure probing and difficulties in probing long RNAs. To fully assess the impact of RNA structure in biology, I aim to utilize and extend high throughput ways to probe RNA structures in solution by coupling structure probing to high throughput sequencing. This enables us to probe RNA structures for thousands of RNAs simultaneously. This expansion of RNA structural data will likely enhance our understanding of how RNA function in different cellular systems, as well as open doors to potentially targeting these structural elements in diseases.

Selected Publications

• Wang J, Yang L, Cheng A, Tham CY, Tan W, Darmawan J, de Sessions PF, Wan Y. Direct RNA sequencing coupled with adaptive sampling enriches RNAs of interest in the transcriptome. Nature Communications. 2024 Jan 11;15(1):481. doi: 10.1038/s41467-023-44656-3. PMID: 38212309.
• Wang J, Zhang Y, Zhang T, Tan WT, Lambert F, Darmawan J, Huber R, Wan Y. RNA structure profiling at single-cell resolution reveals new determinants of cell identity. Nature Methods. 2024 Jan 4. doi: 10.1038/s41592-023-02128-y. Epub ahead of print. PMID: 38177506.
• Liao KC, Xie X, Sundstrom AKB, Lim XN, Tan KK, Zhang Y, Zou J, Bifani AM, Poh HX, Chen JJ, Ng WC, Lim SY, Ooi EE, Sessions OM, Tay Y, Shi PY, Huber RG, Wan Y. Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells. Genome Biology. 2023 Dec 5;24(1):279. doi: 10.1186/s13059-023-03110-9. PMID: 38053173; PMCID: PMC10696742.
• Nagorska A, Zaucker A, Lambert F, Inman A, Toral-Perez S, Gorodkin J, Wan Y, Smutny M, Sampath K. Translational control of furina by an RNA regulon is important for left-right patterning, heart morphogenesis and cardiac valve function. Development. 2023 Dec 1;150(23):dev201657. doi: 10.1242/dev.201657. Epub 2023 Nov 30. PMID: 38032088; PMCID: PMC10730018.
• Chin WX, Kong HY, Zhu IXY, Teo ZY, Faruk R, Lee RCH, Ho SX, Aw ZQ, Yi B, Hou XJ, Tan AKY, Yogarajah T, Huber RG, Cai Y, Wan Y, Chu JJH. Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes. PLoS Pathogens, 2023 Oct 26;19(10):e1011753.
• Walters BW, Tan TJ, Tan CT, Dube CT, Lee KT, Koh J, Ong YHB, Tan VXH, Jahan FRS, Lim XN, Wan Y, Lim CY. Divergent functions of histone acetyltransferases KAT2A and KAT2B in keratinocyte self-renewal and differentiation. J Cell Sci. 2023 Jun 15;136(12):jcs260723. doi: 10.1242/jcs.260723. Epub 2023 Jun 21.
• Priscilla L S Boon, Ana S Martins, Xin Ni Lim, Francisco J Enguita, Nuno C Santos, Peter J Bond, Yue Wan, Ivo C Martins, Roland G Huber. Dengue Virus Capsid Protein Facilitates Genome Compaction and Packaging. International Journal of Molecular Sciences, 2-May-23
• Mattick JS, Amaral PP, Carninci P, Carpenter S, Chang HY, Chen LL, Chen R, Dean C, Dinger ME, Fitzgerald KA, Gingeras TR, Guttman M, Hirose T, Huarte M, Johnson R, Kanduri C, Kapranov P, Lawrence JB, Lee JT, Mendell JT, Mercer TR, Moore KJ, Nakagawa S, Rinn JL, Spector DL, Ulitsky I, Wan Y, Wilusz JE, Wu M. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol. 2023 Jan 3. doi: 10.1038/s41580-022-00566-8.
• Nguyen TA, Heng JWJ, Kaewsapsak P, Kok EPL, Stanojević D, Liu H, Cardilla A, Praditya A, Yi Z, Lin M, Aw JGA, Ho YY, Peh KLE, Wang Y, Zhong Q, Heraud-Farlow J, Xue S, Reversade B, Walkley C, Ho YS, Šikić M, Wan Y, Tan MH. Direct identification of A-to-I editing sites with nanopore native RNA sequencing. Nat Methods. 2022 Jul;19(7):833-844. doi: 10.1038/s41592-022-01513-3. Epub 2022 Jun 13. PMID: 35697834.
• Yang SL, Ponti RD, Wan Y*, Huber RG*. Computational and Experimental Approaches to Study the RNA Secondary Structures of RNA Viruses. Viruses. 2022 Aug 16;14(8):1795. doi: 10.3390/v14081795. PMID: 36016417; PMCID: PMC9415818.
• Xu B, Zhu Y, Cao C, Chen H, Jin Q, Li G, Ma J, Yang SL, Zhao J, Zhu J, Ding Y, Fang X, Jin Y, Kwok CK, Ren A, Wan Y, Wang Z, Xue Y, Zhang H, Zhang QC, Zhou Y. Recent advances in RNA structurome. Sci China Life Sci. 2022 Jul;65(7):1285-1324. doi: 10.1007/s11427-021-2116-2. Epub 2022 Jun 14. PMID: 35717434; PMCID: PMC9206424.
• Rachel Patton McCord, Mikko Taipale, Sarah Teichmann, Rebecca Vorhees, Yue Wan, Cees Dekker, Neville E. Sanjana.  Voices on technology: The molecular biologist’s ever-expanding toy box. Molecular Cell. 22 Jan 20;82(2):221-226. doi: 10.1016/j.molcel.2021.12.025.
• Zhu B, Finch-Edmondson M, Leong KW, Zhang X, V M, Lin QXX, Lee Y, Ng WT, Guo H, Wan Y, Sudol M, DasGupta R. LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer. Cell Death Discov. 2021 Nov 29;7(1):369. doi: 10.1038/s41420-021-00761-0. PMID: 34845189; PMCID: PMC8630011.
• Jiaxu Wang, Tong Zhang, Zhang Yu, Wen Ting Tan, Ming Wen, Yang Shen, Finnlay R.P. Lambert, Roland G. Huber, Yue Wan. Genome-wide RNA structure changes during human neurogenesis modulate gene regulatory networks. Molecular Cell. 2021 Oct 12;S1097-2765(21)00796-6. doi: 10.1016/j.molcel.2021.09.027.
• Siwy Ling Yang, Louis DeFalco, Danielle E. Anderson, Yu Zhang, Ashley J Aw, Su Ying Lim, Xin Ni Lim, Kiat Yee Tan, Tong Zhang, Tanu Chawla, Yan Su, Alexander Lezhava, Andres Merits, Lin-Fa Wang^*, Roland G. Huber^*, Yue Wan^*. Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions. Nature Communications.  2021 Aug 25;12(1):5113. doi: 10.1038/s41467-021-25357-1.
• Yue Zhao, Jiaxu Wang, Wai Nam Liu, Shin Yie Fong, Timothy Wai Ho Shuen, Min Liu, Sarah Harden, Sue Yee Tan, Jia Ying Cheng, Wilson Wei Sheng Tan, Jerry Kok Yen Chan, Cheng Ean Chee, Guan Huei Lee, Han Chong Toh, Seng Gee Lim, Yue Wan, Qingfeng Chen. Analysis and Validation of Human Targets and Treatments Using a Hepatocellular Carcinoma-Immune Humanized Mouse Model. Hepatology. 2021 Sep;74(3):1395-1410. doi: 10.1002/hep.31812.
• Bowen Zhu, Mitheera V, Megan Finch-Edmondson, Yaelim Lee, Yue Wan, Marius Sudol, Ramanuj DasGupta. miR-582-5p Is a Tumor Suppressor microRNA Targeting the Hippo-YAP/TAZ Signaling Pathway in Non-Small Cell Lung Cancer. Cancers (Basel). 2021 Feb 11;13(4):756. doi: 10.3390/cancers13040756.
• Jong Ghut Ashley Aw, Shaun W. Lim, Jia Xu Wang, Yang Shen, Pornchai Kaewsapsak, Eng Piew Louis Kok, Chenhao Li, Boon Si Ng, Leah A. Vardy, Meng How Tan, Niranjan Nagarajan^Ɨ, Yue Wan^Ɨ. Determination of isoform-specific RNA structure with nanopore long reads. Nature Biotechnology,  2020, Nov 12. doi: 10.1038/s41587-020-00755-w.
• Roland G Huber, Jan K Marzinek, Priscilla L S Boon, Wan Yue, Peter J Bond. Computational modelling of flavivirus dynamics: The ins and outs. Methods. 2021 Jan;185:28-38. doi: 10.1016/j.ymeth.2020.06.004. Epub 2020 Jun 8.
• Grzegorz Kudla, Yue Wan and Aleksandra Helwak. RNA Conformation capture by proximity ligation. 2020.  Annual Review of Genomics and Human Genetics, https://doi.org/10.1146/annurev-genom-120219-073756
• Cedric Chih Shen Tan, Sebastian Maurer-Stroh, Yue Wan, October M Sessions, Paola Florez de Sessions. A novel method for the capture-based purification of whole viral native RNA genomes. AMB express. 2019. 9:45
• Roland G. Huber, Xin Ni Lim, Wy Ching Ng, Adelene Y. L. Sim, Hui Xian Poh, Yang Shen, Su Ying Lim, Karin B. Sundstrom, Xuyang Sun, Jong Ghut Aw, Horng Khit Too, Peng Hee Boey, Andreas Wilm, Tanu Chawla, Ming M. Choy, Lu Jiang, Paola Florez de Sessions, Xian Jun Loh, Sylvie Alonso, Martin Hibberd, Niranjan Nagarajan, Eng Eong Ooi, Peter J. Bond, October M. Sessions, Yue Wan. Structure mapping of dengue and Zika viruses reveals functional long-range interactions. 2019. Nature Communications, Mar 29;10(1):1408.
• Sidika Tapsin, Miao Sun, Yang Shen, Huibin Zhang, Xin Ni Lim, Teodorus Theo Susanto, Siwy Ling Yang, Gui Sheng Zeng, Jasmine Lee, Alexander Lezhava, Ee Lui Ang, Lian Hui Zhang, Yue Wang, Huimin Zhao, Niranjan Nagarajan, Yue Wan (2018) Genome-wide identification of natural RNA aptamers in prokaryotes and eukaryotes.  Nature Communications, 2018 Mar 29;9(1):1289.
• Jong Ghut Ashley Aw, Yang Shen, Niranjan Nagarajan, Yue Wan (2017) Mapping RNA-RNA interactions globally using biotinylated psoralen.  J Vis Exp. 2017 May 24;(123).
  
• Minh N. Nguyen, Adelene Y. L. Sim, Yue Wan, M. S. Madhusudhan and Chandra Verma (2016) Topology independent comparison of RNA 3D structures using the CLICK algorithm. Nucleic Acids Research, doi: 10.1093/nar/gkw819
  
• Jong Ghut Ashley Aw¹*, Andreas Wilm²*, Miao Sun²*, Yang Shen², Xin Ni Lim¹, Kum-Loong Boon¹, Yun-Shen Chan³, Tong Zhang⁴, Sidika Tapsin¹, Teodorus Theo Susanto¹, Niranjan Nagarajan²Ɨ, Yue Wan¹Ɨ (2016) In vivo mapping of eukaryotic RNA interactomes reveals principles of higher-order organization and regulation. Molecular Cell 2016 May 19;62(4):603-17
  
• Huibin Zhang, Teodorus T Susanto, Yue Wan, Swaine L. Chen (2016) Comprehensive mutagenesis of fimS reveals novel regulation of Type 1 pili in uropathogenic Escherichia coli. PNAS, 2016 Apr 12;113(15):4182-7.
  
• Yue Wan*ᶧ, Kun Qu*, Qiangfeng Cliff Zhang, Ohad Manor, Zhenqgqing Ouyang, Jiajing Zhang, Michael P. Snyder, Eran Segal and Howard Y. Changᵼ. (2013) Landscape and variation of RNA secondary structure across the human transcriptome. Nature 2014 Jan 30;505(7485):706-9.
  *These authors contributed equally. ᶧ Co-corresponding authors.
• Ibrahim Avsar IIik, Jeffrey J Quinn, Plamen Georgiev, Filipe Tavares-Cadete, Daniel Maticzka, Sarah Toscano, Yue Wan, Robert C. Spitale, Nicholar Luscombe, Rolf Backofen, Howard Y. Chang and Asifa Akhtar. (2013)Tandem Stem-Loops in roX RNAs Act Together to Mediate X Chromosome Dosage Compensation in Drosophila. Molecular Cell 2013 Jul 25;51(2):156-73.
  
• Yue Wan, Kun Qu, Zhengqing Ouyang and Howard Y. Chang. (2013) Genome-wide mapping of RNA structure using nuclease digestion and high-throughput sequencing. Nature Protocols, 2013 May;8(5):849-69.
  
• Man Zhang, Lili Li, Zhongfeng Wang, Huijuan Liu, Junlin Hou, Min Zhang, Aijun Hao, Yun Liu, Guang He, Yongyong Shi, Lin He, Xueying Wang, Yue Wan* and Baojie Li* (2012). A role for c-Abl in cell senescence and spontaneous immortalization. AGE 10.1007/s11357-012-9452-4.  *corresponding author
• Karen M. Chisholm, Yue Wan, Rui Li, Kelli D. Montgomery, Howard Y. Chang and Robert B. West. (2012) Detection of long non-coding RNA in archival tissue: correlation with polycomb protein expression in primary and metastatic breast carcinoma. PLoS One 2012;7(10):e47998.
  
• Yue Wan, Kun Qu, Michael Kertesz, Zhengqing Ouyang, Jun Li, Robert Tibshirani, Robert C. Nutter, Eran Segal, Howard Y. Chang. (2012) Genome-wide measurement of RNA folding energies. Molecular Cell 48(2):169-81. 
• Yue Wan, Michael Kertesz, Robert C. Spitale, Eran Segal and Howard Chang. (2011) Understanding the transcriptome through RNA structure. Nature Reviews Genetics 12(9):641-55.
  
• Yue Wan and Howard Chang. (2010) HOTAIR: Flight of noncoding RNAs in cancer metastasis.  Cell Cycle 9(17):3391-2
  
• Michael Kertesz*, Yue Wan*, Elad Mazor, John L. Rinn, Robert C. Nutter, Howard Y. Chang, Eran Segal. (2010) Genome-wide Measurement of RNA Secondary Structure in Yeast.  Nature 467(7311):103-7.   * these authors contributed equally.
  
• Miao-Chih Tsai, Ohad Manor, Yue Wan, Nima Mosammaparast, Jordan K. Wong, Fei Lan, Yang Shi, Eran Segal, Howard Y. Chang. (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329(5992):689-93.