Hong Li Laboratory

Structural Mechanisms and Therapeutics of RNA Biology

The lab of Dr. Hong Li employs cryo-EM and other leading-edge techniques to understand the mechanisms that drive RNA-centric processes such as translation, CRISPR-Cas immunity, pre-RNA splicing and RNA therapeutics. Our lab’s work has far-reaching implications for understanding the role of RNA in health and informing new diagnostic and treatment strategies for cancer and other diseases.

Ribosomes are megadalton “machines” made of RNA and proteins that synthesize proteins, the workhorses that sustain the lives of cells. Making ribosomes is a demanding process, consuming more than 70% of the cell’s energy and involving more than 200 factors. The centrality of ribosome production and its link to cancers makes it an attractive target for anti-cancer drugs. Our lab delves into the innerworkings of ribosomes and their production, aiming to unlock the fundamental mechanisms of this process and identify potential therapeutic targets.

CRISPR-Cas is a bacterial system, also powered by RNA, that promotes host survival and has recently revolutionized genome manipulation for both research and clinical purposes. Our lab investigates several parts of this remarkable system with current focuses on CRISPR-Cas9 and CRISPR-Csm/Cmr. Our goal is to develop next-generation genome manipulation tools that are sensitive to epigenetic marks and diagnosis strategies based on nucleic acids and their modifications.

Selected Publications

For a full list of Dr. Li’s publications, please visit PubMed.

Goswami HN, Ahmadizadeh F, Wang B, Addo-Yobo D, Zhao Y, Whittington AC, He H, Terns MP, Li H. 2024. Molecular basis for cA₆ synthesis by a type III-A CRISPR-Cas enzyme and its conversion to cA₄ production. Nucleic Acid Res.

Das A, Rai J, Roth MO, Shu Y, Medina ML, Barakat MR, Li H. 2023. Coupled catalytic states and the role of metal coordination in Cas9. Nat Catal 6:969–977.

Zhao Y, Rai J, Li H. 2023. Regulation of translation by ribosomal RNA pseudouridylation. Science Adv 9(33).

Goswami HN, Rai J, Das A, Li H. 2022. Molecular mechanism of active Cas7-11 in processing CRISPR RNA and interfering target RNA. eLife 11:e81678.
*Featured on cover

Roth MO, Li H. 2022. “X” marks the spot: Mining the gold in CasX for gene editing. Mol Cell 82(6):1083–1085.

Zhao Y, Rai J, Yu H, Li H. 2022. CryoEM structures of pseudouridine-free ribosome suggest impacts of chemical modifications on ribosome conformations. Structure 30:1–10.

Sridhara S, Goswami HN, Whyms C, Dennis JH, Li H. 2021. Virus detection via programmable Type III-A CRISPR-Cas systems. Nature Comm 12(1):5653.
*Highlighted in SpringerNature Research Communities

Das A, Hand TH, Smith CL, Wickline E, Zawrotny M, Li H. 2020. The molecular basis for recognition of 5′-NNNCC-3′ PAM and its methylation state by Acidothermus cellulolyticus Cas9. Nature Comm 11(1):6346.

Tian S, Yu G, He H, Zhao Y, Liu P, Marshall AG, Demeler B, Stagg SM, Li H. 2017. Pih1p-Tah1p puts a lid on hexameric AAA+ ATPases Rvb1/2p. Structure 25(10):1519–1529.

Tsui TK, Li H. 2015. Structure principles of CRISPR-Cas surveillance and effector complexes. Ann Rev Biophys 44:229–255.

Hale CR, Cocozaki A, Li H, Terns RM, Terns MP. 2014. Target RNA capture and cleavage by the Cmr type III-B CRISPR-Cas effector complex. Genes Dev 28: 2432–2443.

Spilman M, Cocozaki A, Hale C, Shao Y, Ramia N, Terns R, Terns M, Li H, Stagg S. 2013. Structure of an RNA silencing complex of the CRISPR-Cas immune system. Mol Cell 52:146–152.

Xue S, Wang R, Yang F, Terns RM, Terns MP, Zhang X, Maxwell ES, Li H. 2010. Structural basis for substrate placement by an archaeal box C/D ribonucleoprotein particle. Mol Cell 39, 939–949.

Liang B, Zhou J, Kahen E, Terns RM, Terns MP, Li H. 2009. Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA. Nat Struct Mol Biol 16:740–746.

Carte J, Wang R, Li H, Terns RM, Terns MP. 2008. Cas6 Is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes. Genes Dev 22(24):3489–3496.

Liang B, Xue S, Terns RM, Terns MP, Li H. 2007. Substrate RNA positioning in the archaeal H/ACA ribonucleoprotein complex. Nat Struct Mol Biol 14:1189–1195.

Li H. 2007. Complexes of tRNA and maturation enzymes: shaping up for translation. Curr Opin Struct Biol 17: 293–301.

Xue S, Calvin K, Li H. 2006. RNA recognition and cleavage by a splicing endonuclease. Science 312:906 –910 (2006).

Trotta CR, Paushkin SV, Patel M, Li H, Peltz SW. 2006. Cleavage of pre-tRNAs by the splicing endonuclease requires a composite active site. Nature 441:375–377.

Rashid R, Liang B, Baker DL, Youssef OA, He Y, Phipps K, Terns RM, Terns MP, Li H. 2006. Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided pseudouridylation and dyskeratosis congenita. Mol Cell 21:249–260.

Aittaleb M, Rashid R, Chen Q, Palmer JR, Daniels CJ, Li H. 2003. Structure and function of archaeal box C/D sRNP core proteins. Nat Struct Mol Biol 10:256–263.