Shouhong Guang is a chair professor at the University of Science and Technology of China (USTC). He graduated from USTC with bachelor and master degrees and then a Ph.D. degree from the University of Wisconsin-Madison with Professor Janet Mertz. He did his postdoc training with Professor Scott Kennedy and came back to USTC to set up his own lab in 2010. His research has been focusing on the mechanism and function of small regulatory RNAs in C. elegans and has discovered the nuclear RNAi defective pathway, a new class of siRNAs and nucleolar RNAi, and the protein machineries for piRNA transcription and processing. Meanwhile, he investigated the mechanism of transgenerational inheritance of RNAi. He was awarded the one hundred talents and one thousand young elite programs.

Research Achievements:

The mechanistic underpinnings of RNAi are broadly conserved across eukaryotes. Initial successes utilizing small RNAs to target oncogenic and viral mRNAs have generated excitement that small RNAs may eventually be utilized to treat human diseases. Prior to the rational use of small RNAs in therapeutics, it is essential to understand their biogenesis, specificity, transportation, and endogenous roles.

I am very interested in how small RNAs are generated, transported and regulated, and how they function in the nucleus in metazoan, especially in the model organism C. elegans. To address these questions, our lab applied forward and reverse genetics, in addition to proteomic approaches, to identify factors required for nuclear and nucleolar RNAi, and the biogenesis of small regulatory RNAs. We have discovered the nuclear RNAi defective (NRDE) pathway (Science 2008; Nature 2010; PLoS Genetics 2011; Genetics 2014; Current Biology 2015), a class of antisense ribosomal siRNAs (risiRNAs) and nucleolar RNAi (Nature Structural & Molecular biology 2017; PNAS 2018; Nucleic Acids Research 2021a), the protein machineries for piRNA transcription and processing (USTC complex, UAD-2, PICS complex) (Genes & Development 2019; Cell Reports 2019; PNAS 2021; Nature Communications 2021; Journal of Genetics and Genomics 2022). Meanwhile, we found that both nuclear and cytoplasmic machineries are required for transgenerational inheritance of RNAi (Nature Genetics 2012; Cell Reports 2018). The mechanism of epigentics mediated lifespan regulation (Elife 2022). We have also developed the gene editing method in C. elegans (Scientific Reports 2014; Genetics 2015; G3 2018).

Selected Publications

Meng Huang(#), Minjie Hong(#), Chengming Zhu, Di Chen(*), Xiangyang Chen(*), Shouhong Guang(*), and Xuezhu Feng(*) (2022) H3K9me1/2 methylation limits the lifespan of daf-2 mutants in C. elegans. Elife. 2022 Sep 20;11:e74812. doi: 10.7554/eLife.74812.

Xuelian Ma(#), Shumin Cheng(#), Ruofan Ding, Zhaozhao Zhao, XuDong Zou, Shouhong Guang, Qixuan Wang, Huan Jing, Chen Yu, Ting Ni, Lei Li(*) (2022)  ipaQTL-atlas: an atlas of intronic polyadenylation quantitative trait loci across human tissues. Nucleic Acids Research, 2022 Aug 31, https://doi.org/10.1093/nar/gkac736

Xinhao Hou(#), Chengming Zhu, Mingjing Xu, Xiangyang Chen, Cheng Sun, Björn Nashana(*), Shouhong Guang(*), and Xuezhu Feng(*) (2022) The SNAPc complex mediates starvation-induced trans-splicing in C. elegans. Journal of Genetics and Genomics, 2022 Mar 10:S1673-8527(22)00076-5. doi: 10.1016/j.jgg.2022.02.024.

Xiaoyang Wang(#), Chenming Zeng(#), Shanhui Liao(#), Zhongliang Zhu, Jiahai Zhang, Xiaoming Tu, Xuebiao Yao, Xuezhu Feng(*), Shouhong Guang(*), and Chao Xu(*) (2021) Molecular basis for PICS-mediated piRNA biogenesis and cell division. Nature Communications, 2021 Sep 22;12(1):5595. doi: 10.1038/s41467-021-25896-7

Shimiao Liao(#), Xiangyang Chen(#), Ting Xu(#), Qile Jin, Zongxiu Xu, Demin Xu, Xufei Zhou, Chengming Zhu(*), Shouhong Guang(*) and Xuezhu Feng(*) (2021a) Antisense ribosomal siRNAs inhibit RNA polymerase I-directed transcription in C. elegans Nucleic Acids Research 2021 Sep 20;49(16):9194-9210. doi: 10.1093/nar/gkab662.

Zheng Xu(#), Jie Zhao, Minjie Hong, Chenming Zeng, Shouhong Guang(*), Yunyu Shi(*) (2021b) Structural recognition of the mRNA 3’ UTR by PUF-8 restricts the lifespan of C. elegans. Nucleic Acids Research, 2021 Sep 27;49(17):10082-10097. doi: 10.1093/nar/gkab754

Xinya Huang(#), Peng Cheng(#), Chenchun Weng, Zongxiu Xu, Chenming Zeng, Xiangyang Chen(*), Chengming Zhu(*), Shouhong Guang(*), and Xuezhu Feng(*) (2021) A chromodomain protein mediates heterochromatin-directed piRNA expression. PNAS, 2021 Jul 6;118(27):e2103723118. doi: 10.1073/pnas.2103723118

Chenming Zeng (#), Chenchun Weng (#), Xiaoyang Wang (#), Yong-Hong Yan (#), Wen-Jun Li, Demin Xu, Minjie Hong, Shanhui Liao, Meng-Qiu Dong, Xuezhu Feng (*), Chao Xu (*), and Shouhong Guang (*) (2019) Functional proteomics identifies a PICS complex required for piRNA maturation and chromosome segregation. Cell Reports 2019 Jun 18;27(12):3561-3572.e3. doi: 10.1016/j.celrep.2019.05.076

Chenchun Weng (#), Joanna Kosalka (#), Ahmet C. Berkyurek (#), Przemyslaw Stempor, Xuezhu Feng, Hui Mao, Chenming Zeng, Wen-Jun Li, Yong-Hong Yan, Meng-Qiu Dong, Natalia Rosalía Morero, Cecilia Zuliani, Orsolya Barabas, Julie Ahringer, Shouhong Guang (*), and Eric A. Miska (*) (2019) The USTC complex co-opts an ancient machinery to drive piRNA transcription in C. elegans. Genes & Development2019 Jan 1;33(1-2):90-102. doi: 10.1101/gad.319293.118. Epub 2018 Dec 19.

Chengming Zhu (#), Qi Yan (#), Chenchun Weng, Xinhao Hou, Hui Mao, Dun Liu, Xuezhu Feng (*), Shouhong Guang (*) (2018) Erroneous ribosomal RNAs promote the generation of antisense ribosomal siRNA. PNAS 2018 Oct 2;115(40):10082-10087. doi: 10.1073/pnas.1800974115.

Chen X (#*), Liao S (#), Huang X, Xu T, Feng X, Guang Shouhong (*). (2018) Targeted Chromosomal Rearrangements via a Combinatorial Use of CRISPR/Cas9 and Cre/LoxP Technologies in Caenorhabditis elegans. G3 (Bethesda). 2018 Jul 31;8(8):2697-2707. doi: 10.1534/g3.118.200473.

Fei Xu (#), Xuezhu Feng (#), Xiangyang Chen, Chenchun Weng, Qi Yan, Ting Xu, Minjie Hong, and Shouhong Guang (*)（2018）A cytoplasmic Argonaute protein promotes the inheritance of RNAi. Cell Reports. 2018 May 22;23(8):2482-2494. doi: 10.1016/j.celrep.2018.04.072

Zhou X (#), Chen X (#), Wang Y, Feng X (*), Shouhong Guang (*). (2017) A new layer of rRNA regulation by small interference RNAs and the nuclear RNAi pathway. RNA Biol.2017 Nov 2;14(11):1492-1498. doi: 10.1080/15476286.2017.1341034. [Epub ahead of print]

Xufei Zhou (#), Xuezhu Feng (#), Hui Mao, Mu Li, Fei Xu, Kai Hu, and Shouhong Guang(*)  (2017) RdRP-synthesized antisense ribosomal siRNAs silence pre-rRNA via the nuclear RNAi pathway. Nature Structural & Molecular Biology2017 Mar;24(3):258-269. doi: 10.1038/nsmb.3376.

Li G, Wu X, Qian W, Cai H, Sun X, Zhang W, Tan S, Wu Z, Qian P, Ding K, Lu X, Zhang X, Yan H, Song H, Guang Shouhong, Wu Q, Lobie PE, Shan G, Zhu T.(2016) CCAR1 5' UTR as a natural miRancer of miR-1254 overrides tamoxifen resistance. Cell Research 2016 Jun;26(6):655-73. doi: 10.1038/cr.2016.32.

Chen X (#), Li M (#), Feng X (*), Shouhong Guang (*) (2015) Targeted Chromosomal Translocations and Essential Gene Knockout Using CRISPR/Cas9 Technology in Caenorhabditis elegans.Genetics 2015 Dec;201(4):1295-306 doi: 10.1534/genetics.115.181883.

Hui Mao (#), Chengming Zhu (#), Dandan Zong, Chenchun Weng, Xiangwei Yang, Hui Huang, Dun Liu, Xuezhu Feng (*), and Shouhong Guang (*) (2015) The Nrde pathway mediates small RNA-directed histone H3 lysine 27 trimethylation in Caenorhabditis elegans. Current Biology2015 Sep 21;25(18):2398-403. doi: 10.1016/j.cub.2015.07.051. Epub 2015 Sep 10.

Xiangyang Chen (#), Fei Xu (#), Chengming Zhu, Jiaojiao Ji, Xufei Zhou, Xuezhu Feng (*), and Shouhong Guang (*) (2014) Dual sgRNA-directed gene knockout using CRISPR/Cas9 technology in Caenorhabditis elegans. Scientific Reports2014 Dec 22;4:7581. doi: 10.1038/srep07581.

Zhou X (#), Xu F (#), Mao H, Ji J, Yin M, Feng X (*), and Shouhong Guang (*) (2014) Nuclear RNAi Contributes to the Silencing of Off-Target Genes and Repetitive Sequences in Caenorhabditis elegans. Genetics2014 May;197(1):121-32. doi: 10.1534/genetics.113.159780.

Xuezhu Feng and Shouhong Guang(*) (2013) Small RNAs, RNAi and the Inheritance of Gene Silencing in Caenorhabditis elegans. Journal of Genetics and Genomics 2013，Apr 20;40(4):153-60. doi: 10.1016/j.jgg.2012.12.007. Epub 2013 Feb 4. Review.

Sam Guoping Gu, Julia Pak, Shouhong Guang, Jay M. Maniar, Scott Kennedy, and Andrew Fire, (2012) Amplification of siRNA in Caenorhabditis elegans generates a transgenerational sequence-targeted histone H3 lysine 9 methylation footprint. Nature Genetics 2012，Jan 8;44(2):157-64. doi: 10.1038/ng.1039..

Burkhart, K.B., Guang, Shouhong, Bochner, A.F., and Kennedy, S., (2011) A pre-mRNA–associating factor links endogenous siRNAs to chromatin regulation. PLoS Genetics, 2011 Aug;7(8):e1002249. doi: 10.1371/journal.pgen.1002249. Epub 2011 Aug 25..

Guang, Shouhong (#), Bochner, A.F., Pavelec, D.M., Burkhart, K.B., Burton, N., and Kennedy, S., (2010) Small regulatory RNAs inhibit RNA Polymerase II during the elongation phase of transcription. Nature, 2010，Jun 24;465(7301):1097-101. doi: 10.1038/nature09095. Epub 2010 Jun 13.

Guang, Shouhong (#), Bochner, A.F. (#), Pavelec, D.M., Burkhart, K.B., Harding, S., Lachowiec, J., and Kennedy, S., (2008) An Argonaute transports siRNAs from the cytoplasm to the nucleus. Science Jul 25;321(5888):537-41. doi: 10.1126/science.1157647. Erratum in: Science. 2009 Dec         

Guang, Shouhong, Felthauser, A., and Mertz, J. (2005) Binding of hnRNP L to the pre-mRNA processing enhancer (PPE) of herpes simplex virus’ thymidine kinase gene enhances both polyadenylation and nucleocytoplasmic export of intronless mRNAs. Mol. Cell. Biol.Aug;25(15):6303-13.

Guang, Shouhong and Mertz, J.E. (2005) PPE-like elements from intronless genes play additional roles in mRNA biogenesis than do ones from intron-containing genes. Nucleic Acid Res.Apr 20;33(7):2215-26. Print 2005.