Focus: Genetics, Metabolism, and Genome Editing of Anaerobic Microorganisms 

Research Overview and Significance 

Anaerobic microorganisms play critical roles in global carbon cycling, energy conversion, and human gut health. Studying these organisms provides key insights into life’s adaptation to extreme environments and supports the development of novel green bioenergy and biomanufacturing technologies. Among them, methanogenic archaea are of particular importance due to their ecological functions in Earth’s carbon cycle, greenhouse gas dynamics, and organic waste valorization. These organisms are central not only to environmental, agricultural, and human-animal health interfaces but also serve as a representative lineage of Archaea, the third domain of life, offering unique opportunities to explore archaeal biology and one-carbon biotransformation technologies. 

Our group focuses on methanogenic archaea and related anaerobic microbes to systematically uncover new pathways and mechanisms by which they drive global carbon cycling. Based on mechanistic insights, we aim to inform strategies for controlling methane emissions and advancing bioenergy production. We investigate novel genetic and transcriptional regulatory mechanisms in Archaea to establish new paradigms of gene regulation in prokaryotes, thereby contributing to our understanding of the evolution of genetic systems and the origin of eukaryotes. Additionally, we develop new genome editing tools and functional genetic elements for anaerobic microorganisms, promoting their applications in environmental remediation, host-associated health, and sustainable biomanufacturing.

2000-July 2004, B.S. Sept., Northwest A&F University, China 

Sept. 2004-July 2010, M.S. & Ph.D. (integrated program), Institute of Microbiology, Chinese Academy of Sciences (IMCAS), China

July 2010-Sept. 2017, Assistant Professor, Institute of Microbiology, Chinese Academy of Sciences China 

Sept. 2017-Oct. 2023, Associate Professor, Institute of Microbiology, Chinese Academy of Sciences, China 

Since Dec. 2021, Selected as a Member of the First Cohort of CAS Distinguished Research Fellows Since Nov. 2023, Professor, Institute of Microbiology, Chinese Academy of Sciences, China

Dr. Jie Li has long focused on the fundamental mechanisms of genetic regulation and environmental adaptation in extremophilic anaerobes—particularly methanogenic archaea—and on the discovery and development of functional genetic elements. Her research has led to a series of original findings that have significantly advanced mechanistic understanding and enabled the engineering of anaerobic microbial platforms. 

The major achievements can be summarized in three interconnected areas: 

1. Discovery of novel transcriptional regulatory paradigms in prokaryotes, revealing their roles in controlling key physiological processes and offering new strategies for prokaryotic gene expression control.
2. Identification of previously unknown transcriptional and post-transcriptional regulatory factors, along with mechanistic insights into their functions, thus opening new research frontiers in archaeal RNA biology.
3. Systematic development of molecular parts and gene-editing tools for extremophilic anaerobes, resulting in specialized archaeal chassis, efficient genome editing systems, and comprehensive libraries of regulatory elements. These innovations lay a foundation for the sustainable biotechnological application of methanogenic archaea.
Dr. Jie Li has published nearly 40 peer-reviewed articles, including over 20 high-impact papers as first and/or corresponding author in leading journals such as Trends Microbiol (2025), Nat Chem Biol (2024), Cell Host Microbe (2023), Nucleic Acids Res (2017, 2020, 2023), Metab Eng (2023), eLife (2021), Curr Res Biotechnol (2023), Environ Microbiol (2021), PLoS Genet (2019), RNA Biol (2023, 2020a, 2020b), Mol Microbiol (2017), with a cumulative impact factor exceeding 180. Her research in archaeal genetics and gene editing has reached an internationally competitive level with broad recognition in the field.

[1] Jie Li*, #, Yueting Liang #, Xiuzhu Dong *. Post-transcriptional regulation in archaea. Trends Microbiol. 2025 Jul;33(7):765-781. doi: 10.1016/j.tim.2025.02.004. 

[2] Xian Shu#, Rui Wang#, Zhihua Li#, Qiong Xue#, Jiajun Wang, Jingfang Liu, Feiyue Cheng, Chao Liu, Huiwei Zhao, Chunyi Hu, Jie Li*, Songying Ouyang*, Ming Li*, CRISPR-repressed toxin-antitoxin provides population-level immunity against diverse anti-CRISPR elements. Nat Chem Biol. 2025 Mar;21(3):337-347. doi: 10.1038/s41589-024-01693-3. 

[3] Wenting Zhang, Deron Ren, Zhihua Li, Lei Yue, William B.Whitman, Xiuzhu Dong*, Jie Li*. Internal transcription termination widely regulates differential expression of operon-organized genes including ribosomal protein and RNA polymerase genes in an archaeon. Nucleic Acids Res. 2023 Aug 25;51(15):7851-7867. 

[4] Chao Liu #, Rui Wang #, Jie Li #, Feiyue Cheng #, Xian Shu #, Huiwei Zhao, Qiong Xue, Haiying Yu, Aici Wu, Lingyun Wang, Sushu Hu, Yihan Zhang, Jun Yang, Hua Xiang*, Ming Li*. Widespread RNA-based cas regulation monitors crRNA abundance and anti-CRISPR proteins. Cell Host & Microbe. 2023 31(9):1481-1493. 

[5] Lei Yue #, Jie Li #, *, Bing Zhang, Lei Qi, Zhihua Li, Fangqing Zhao, Lingyan Li, Xiaowei Zheng, Xiuzhu Dong*. The conserved ribonuclease aCPSF1 triggers genome-wide transcription termination of Archaea via a 3′-end cleavage mode. Nucleic Acids Res. 2020, Sep 25;48(17):9589-9605. 

[6] Lei Qi, Lei Yue, Deqin Feng, Fengxia Qi, Jie Li *, and Xiuzhu Dong*. Genome-wide mRNA processing in methanogenic archaea reveals post-transcriptional regulation of ribosomal protein synthesis, Nucleic Acids Res. 2017, Jul 7;45(12):7285-7298. 

[7] Qing Xu, Qing Du, Jian Gao, Lei Chen, Xiuzhu Dong, Jie Li *. A robust genetic toolbox for fine-tuning gene expression in the CO2-Fixing methanogenic archaeon Methanococcus maripaludis. Metab Eng. 2023 Jul 24;79:130-145. 

[8] Jie Li #, *, Lei Yue #, Zhihua Li #, Wenting Zhang, Bing Zhang, Fangqing Zhao, Xiuzhu Dong*. aCPSF1 cooperates with terminator U-tract to dictate archaeal transcription termination efficacy. eLife. 2021 Dec 29;10:e70464. 

[9] Jie Li #, *, Bo Zhang#, Liguang Zhou#, Lei Qi, Lei Yue, Wenting Zhang, Huicai Cheng, William B Whitman*, Xiuzhu Dong*. The archaeal RNA chaperone TRAM0076 shapes the transcriptome and optimizes the growth of Methanococcus maripaludis. PLoS Genet. 2019 Aug 12;15(8):e1008328. 

[10] Du Qing#, Yufei Wei#, Liuyang Zhang#, Derong Ren, Jian Gao, Xiuzhu Dong, Liping Bai*, Jie Li*. An improved CRISPR and CRISPR interference (CRISPRi) toolkit for engineering the model methanogenic archaeon Methanococcus maripaludis. Microb Cell Fact. 2024 Sep 4;23(1):239. doi: 10.1186/s12934-024-02492-0. 

[11] Lei Qi, Huan Liu, Jian Gao, Kai Deng, Xiaoyan Wang, Xiuzhu Dong, Jie Li *. Endonucleolytic processing plays a critical role in the maturation of ribosomal RNA in Methanococcus maripaludis. RNA Biol. 2023 Jan;20(1):760-773. 

[12] Jie Li #, *, Yanjie Hou#, Xien Gu#, Lei Yue, Lu Guo, Defeng Li*, Xiuzhu Dong*. A newly identified duplex RNA unwinding activity of archaeal RNase J depends on processive exoribonucleolysis coupled steric occlusion by its structural archaeal loops. RNA Biol. 2020b, Oct;17(10):1480-1491. 

[13] Jie Li, Taiwo S. Akinyemi, Nana Shao, Can Chen, Xiuzhu Dong, Yuchen Liu, William B. Whitman*. Genetic and metabolic engineering of Methanococcus spp, CURR RES BIOTECHNOL, 5 (2023) 100115 

[14] Jie Li #, *, Liuyang Zhang #, Qing Xu #, Wenting Zhang, Zhihua Li, Lei Chen, Xiuzhu Dong*. CRISPR-Cas9 toolkit for genome editing in an autotrophic CO2 fixing methanogenic archaeon. Microbiol Spectr. 2022. Aug 31;10(4):e0116522. 

[15] Jia Jia#, Jie Li #, *, Lei Qi, Lingyan Li, Lei Yue, Xiuzhu Dong*. Post-transcriptional regulation is involved in the cold active methanol-based methanogenic pathway of a psychrophilic methanogen, Environ Microbiol. 2021 Jul;23(7):3773-3788. doi: 10.1111/1462-2920.15420. 

[16] Jie Li #, Xiaowei Zheng#, Lingyan Li, Shengjie Zhang, Mifang Ren, Li Huang*, Xiuzhu Dong*. The Archaeal Transcription Termination Factor aCPSF1 Is a Robust Phylogenetic Marker for Archaeal Taxonomy. Microbiol Spectr. 2021 Dec 22;9(3):e0153921. 

[17] Xiaoyan Wang#, Xien Gu#, Jie Li #, *, Lei Yue, Defeng Li, Xiuzhu Dong*. Characterization of the Methanomicrobial Archaeal RNase Zs for Processing the CCA-Containing tRNA Precursors. Front Microbiol. 2020, Aug 25;11:1851. 

[18] Lei Qi#,, Jie Li #, *, Jia Jia, Lei Yue, Xiuzhu Dong*. Comprehensive analysis of the pre-ribosomal RNA maturation pathway in a methanoarchaeon exposes the conserved circularization and linearization mode in archaea. RNA Biol. 2020a, Oct;17(10):1427-1441. 

[19] Bo Zhang, Lei Yue, Liguang Zhou, Lei Qi, Jie Li *, Xiuzhu Dong*. The conserved TRAM domain functions as the archaeal cold shock protein via RNA chaperone activity, Front Microbiol. 2017, Aug 22;8:1597. 

[20] Xin Zheng#, Na Feng#, Defeng Li*, Xiuzhu Dong* and Jie Li #, *. New molecular insights into an archaeal RNase J reveal a conserved processive exoribonucleolysis mechanism of the RNase J family, Mol Microbiol. 2017, Nov;106(3):351-366. 

[21] Jie Li #, Lei Qi#, Yang Guo, Lei Yue, Yanping Li, Weizhen Ge, Jun Wu, Wenyuan Shi, Xiuzhu Dong*. Global mapping transcriptional start sites revealed both transcriptional and post-transcriptional regulation of cold adaptation in the methanogenic archaeon Methanolobus psychrophilus, Sci Rep. 2015 Mar 18;5:9209. 

[22] Jie Li #, Xin Zheng#, Xiaopeng Guo, Lei Qi, Xiuzhu Dong*. Characterization of an archaeal two-component system that regulates methanogenesis in Methanosaeta harundinacea, PLoS One. 2014 Apr 18;9(4):e95502. 

[23] Jie Li, Jingfang Liu, Jian Zhou, Hua Xiang*. Functional evaluation of four putative DNA-binding regions in Thermoanaerobacter tengcongensis reverse gyrase, Extremophiles. 2011 Mar;15(2):281-91. 

[24] Jie Li, Jingfang Liu, Ligang Zhou, Huadong Pei, Jian Zhou, Hua Xiang*. Two distantly homologous DnaG primases from Thermoanaerobacter tengcongensis exhibit distinct initiation specificities and priming activities, J Bacteriol. 2010 Jun;192(11):2670-81.