Professor of School of Life Sciences
University of Science & Technology of China
HuangShan Road #443，Anhui Province, Hefei City, 230027
Tel: 86(551) 3607812 (o)
1991-1996 B.S. in Biochemistry and Molecular Biology, University of Science and Technology of China (USTC), China
1996-1999 M.S. in Biochemistry and Molecular Biology, University of Science and Technology of China (USTC), China
1999-2004 Ph.D. in Cancer Biology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison
2005-2010 Postdoctoral fellow in Department of Pharmacology and Department of Genetics, University of Wisconsin, Madison
2011-present Professor, School of Life Sciences, University of Science and Technology of China
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 RNA in therapeutics, it is essential to understand their biogenesis, specificity, transportation, and endogenous roles.
We am very interested in how small RNAs are transported and regulated, and how they function in the nucleus in metazoan. To address these questions, we conducted a genetic screen to identify factors required for nuclear RNAi in the model organism C. elegans and have identified three new genes termed nuclear RNAi defective (NRDE)-1/2/3. We have also identified a bifurcation of the nuclear and cytoplasmic RNAi pathway, a novel small RNA transport pathway, and a novel nuclear gene silencing mechanism.
Our research indicates that metazoans use a different mechanism than A. thaliana and S. pombe to silence gene expression in the nucleus. Further understanding how small RNAs function in the nucleus via NRDEs may permit more stable and specific inhibition of gene expression and facilitate advancement of both basic research and therapeutics.
1. 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 Biology 2017 Feb 6. doi: 10.1038/nsmb.3376.
2. 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.
3. 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 Biology 2015 Sep 21;25(18):2398-403.
4. 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 Reports 2014 Dec. 22;4:7581.
5. Zhou X, Xu F, Mao H, Ji J, Meng Y, Feng X, and Shouhong Guang (2014) Nuclear RNAi Contributes to the Silencing of Off-Target Genes and Repetitive Sequences in Caenorhabditis elegans. Genetics 2014 May;197(1):121-32.
6. 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 2012，44:157-164.
7. Burkhart, K.B., Guang, S., 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.
8. Guang, S., 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, 2010，465:1097-1101.
9. Guang, S., 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 321:537-541 Research Article
10. Guang, S., 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. 25:6303-6313.
11. Guang, S. 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. 33(7):2215-2226.