Chengqi Yi, Ph.D.
Group of nucleic acid modification
Professor, College of Life Sciences, Peking University
tel：
E-mail：chengqi.yi@pku.edu.cn
1.Nucleic acid modification-mediated epigenetic processes
2.The impact of novel RNA modifications to the biological functions of microRNA and large intergenic non-conding RNA (lincRNA)
3.The mechanisms and roles of base-excision repair and nucleotide excision repair in preventing tumor growth and cancer metathesis
In the field of RNA epigenetics
1.Transcriptome-wide Mapping N1-methyladenosine (2016，Nature Chemical Biology）
N1-methyladenosine (m1A) is prevalent in tRNA and rRNA, and it plays an important role in functions of the ncRNAs. Yet little is known about its abundance, topology and dynamics in mRNA. Here, we showed that m1A is prevalent in homo sapiens mRNA, with an m1A/A ratio of ~0.02%. We develop m1A-ID-Seq, based on m1A immunoprecipitation and the inherent property of m1A to stall reverse transcription, for the transcriptome-wide m1A profiling. m1A-ID-Seq identifies 901 m1A peaks (from 600 genes) in mRNA and ncRNA, and reveals a prominent feature of enrichment in the 5’-untranslated region of mRNA transcripts, distinct from that of N6-methyladenosine, the most abundant internal mammalian mRNA modification. Collectively, our approaches allow comprehensive analysis of m1A methylation and provide tools for functional studies of potential epigenetic regulation via the reversible and dynamic m1A methylation. This work has been published in Nature Chemical Biology (doi: 10.1038/nchembio.2040.)
2.Invited review in Nature Methods focus on “Epitranscriptome analysis” (2016, Nature Methods)
In recent years, major breakthroughs in RNA modification-mediated regulation of gene expression have been made, leading to the emerging field of epitranscriptomics or RNA epigenetics. The rapidly evolving field is greatly facilitated by the development of novel epitranscriptome sequencing technologies, which have significantly enriched our understanding of the distribution, regulation and function of these dynamic RNA modifications. In this review, we focus on the major mRNA modifications in the transcriptome of eukaryotic cells, which are N6-methyladenosine (m6A), N6,2’-O-dimethyladenosine (m6Am), 5-methylcytidine (m5C), 5-hydroxylmethylcytidine (hm5C), Inosine (I), pseudouridine (Ψ) and N1-methyladenosine (m1A). We discuss the sequencing technologies of these epitranscriptomic marks in multiple aspects, the existing challenges of epitranscriptome profiling and highlight the prospect of future detection tools. Epitranscriptome analysis is selected as Method of the Year 2016; and two works from our group (（Nat. Chem. Biol. 11, 592–597 (2015) ；Nat. Chem. Biol. 12, 311–316 (2016)) are also introduced in the Method of the Year 2016.
3.Mapping Pseudouridine in the transcriptome level (2015, Nature Chemical Biology)
The modification and function study of pseudouridine in mRNA. Pseudouridine (Ψ) is the most abundant post-transcriptional RNA modification, yet little is known about the prevalence, mechanism and function of Ψ in mRNA. We performed quantitative mass spectrometry analysis and showed that Ψ is much more prevalent (Ψ/U ratio: ~0.2% to 0.6%) in mammalian mRNA than previously believed. We developed CeU-Seq and identify 2,084 Ψ sites within 1,929 human transcripts, of which four are experimentally verified. We show that PUS1 acts on human mRNA; upon stress, the level and location of Ψ are dynamically regulated in stress-specific manners. Comparative analyses of pseudouridylation between human and mouse reveal conserved and unique pseudouridylation sites. We also observe stop codon pseudouridylation and readthrough events simultaneously for mRNA, indicating a role of pseudouridine in nonsense suppression. Collectively, our approaches allow comprehensive analysis of transcriptome-wide pseudouridylation and provide an important resource for functional studies of Ψ-mediated epigenetic regulation. This work has been published in Nature Chemical Biology.
In the field of DNA epigenetics
1.Revealed a novel mechanism of base-excision repair ( 2016, Angewandte Chemie)
NEIL1 is a DNA repair glycosylase guarding the mammalian genome against oxidized DNA bases. As the first enzymes in the base-excision repair pathway, glycosylases must recognize the cognate substrates and catalyze their excision. Here we present crystal structures of human NEIL1 bound to a range of duplex DNA. Together with computational and biochemical analyses, our results suggest that NEIL1 promotes tautomerization of thymine glycol (Tg)—a preferred substrate—for optimal binding in its active site. Moreover, this tautomerization event also facilitates NEIL1-catalyzed Tg excision. To our knowledge, the present example represents the first documented case of enzyme-promoted tautomerization for efficient substrate recognition and catalysis in an enzyme-catalyzed reaction. This work was published in PNAS. DOI: 10.1073/pnas.1604591113.）
2.Revealed the genome-wide cisplatin crosslinking profile (2016, Angewandte Chemie.)
Cisplatin is one of the most important anticancer drugs for a variety of solid tumors. Cisplatin forms covalent adducts with DNA, which is believed to be the primary mechanism of its anticancer effect. However, the genomic distribution pattern of cisplatin-DNA adducts remains unknown, due to the lack of a reliable and sensitive genome-wide method. In order to uncover the genomic distribution of cisplatin-DNA adducts, Our group developed “cisplatin-seq” to identify base-resolution cisplatin crosslinking sites in the human genome. We take advantage of the preferential binding of HMGB1 domain A to distorted DNA structures to selectively enrich cisplatin-modified DNA for high-throughput sequencing. Owing to the ability of cisplatin-DNA adducts to stall DNA synthesis, cisplatin crosslinking sites can be identified at base resolution throughout the genome. With "cisplatin-seq", we successfully provide the first genome-wide profile of cisplatin-DNA adducts at base-resolution. This work has been published in Angewandte Chemie as “Very Important Paper”（DOI : 10.1002/anie.201607380 in the International Edition；DOI : 10.1002/ange.201607380 in the German edition）.
3.Developed a "Bisulfite-free", single-base resolution sequencing method for 5fC at whole-genome scale（2015, Nature Methods）
Cytosine methylation plays a fundamental role in gene expression. Recent discovery of TET-mediated iterative oxidation of 5mC to 5hmC, 5fC and 5caC unveiled the long-sought active demethylation in mammals, but the biological functions of 5mC variants remained elusive. Lacking methods for 5fC and 5caC sequencing was a limit for cytosine methylation study. Based on the specific chemical structure of 5fC, we have developed a selective cyclization-labeling on 5fC, which turned out to be fantastic for 5fC base-resolution sequencing. The labeling makes the method an easy and reliable way for 5fC sequencing. Then we enriched the 5fC genomic fragments with the help of “Click Chemistry”. The resulting NGS data is very exciting. We found more than 20,000 enriched regions in the mESC genome, with C-T mismatch representing the 5fC sites. Meanwhile, we found that 5fC distribution is mainly different from the 5hmC at the single-base resolution, though affinity-based data suggested their similarity. The work is published in the Nat. Methods.
He HQ, Wang YQ, Zhang XT, Li XY, Liu C, Yan DF, Deng HT, Sun WL, Yi CQ, Wang JW. (2024) Age-related noncanonical TRMT6-TRMT61A signaling impairs hematopoietic stem cells. Nat. Aging., 4: 213-230.
Lu L, Zhang XT, Zhou YN, Shi ZK, Xie XW, Zhang XY, Gao LL, Fu AB, Liu C, He B, Xiong XS, Yin YF, Wang QQ, Yi CQ, Li XY. (2024) Base-resolution m5C profiling across the mammalian transcriptome by bisulfite-free enzyme-assisted chemical labeling approach. Mol. Cell, 84: 2984-3000.
Song JH, Zhuang Y, Yi CQ. (2024) Programmable RNA base editing via targeted modifications. Nat. Chem. Biol., 20: 277-290.
Shen WG, Sun HX, Liu C, Yi YP, Hou YK, Xiao Y, Hu YF, Lu B, Peng JY, Wang J, Yi CQ. (2024) GLORI for absolute quantification of transcriptome-wide m6A at single-base resolution. Nat. Protoc., 19: 1252-1287.
He B, Chen YT, Yi CQ. (2024) Quantitative mapping of the mammalian epitranscriptome. Curr. Opin. Genet. Dev., 87: 102212.
Wang YJ, Yang C, Sun HX, Jiang H, Zhang P, Huang Y, Liu ZR, Yu YR, Xu ZY, Xiang HF, Yi CQ. (2024) The role of N6-methyladenosine modification in gametogenesis and embryogenesis: impact on fertility. Genom. Proteom. Bioinform., 22: qzae050.
He B, Yao HJ, Yi CQ. (2024) Advances in the joint profiling technologies of 5mC and 5hmC. RSC Chem. Biol., 5: 500-507.
Yi CQ. (2024) DDX21 is a new player in co-transcriptional RNA modification and functions. Sci. China-Life Sci., 67: 2291-2293.
Zhang ML, Zhang XT, Ma YC, Yi CQ. (2024) New directions for Ψ and m1A decoding in mRNA: deciphering the stoichiometry and function. RNA, 30: 537-547.
Song JH, Luo N, Dong LT, Peng JY, Yi CQ. (2024) RNA base editors: the emerging approach of RNA therapeutics. WIREs RNA, 15: e1844.
Sun HX, Li K, Liu C, Yi CQ. (2023) Regulation and functions of non-m6A mRNA modifications. Nat. Rev. Mol. Cell Biol., 24: 714-731.
Liu C, Sun HX, Yi YP, Shen WG, Li K, Xiao Y, Li F, Li YC, Hou YK, Lu B, Liu WQ, Meng HW, Peng JY, Yi CQ, Wang J. (2023) Absolute quantification of single-base m6A methylation in the mammalian transcriptome using GLORI. Nat. Biotechnol., 41: 355-366.
Song JH, Dong LT, Sun HX, Luo N, Huang Q, Li K, Shen XW, Jiang Z, Lv ZC, Peng LX, Zhang MF, Wang K, Liu K, Hong JX, Yi CQ. (2023) CRISPR-free, programmable RNA pseudouridylation to suppress premature termination codons. Mol. Cell, 83: 139-155.
Lei ZX, Meng HW, Rao XC, Zhao HA, Yi CQ. (2023) Detect-seq, a chemical labeling and biotin pull-down approach for the unbiased and genome-wide off-target evaluation of programmable cytosine base editors. Nat. Protoc., 18: 2221-2255.
Zhang ML, Jiang Z, Ma YC, Liu WQ, Zhuang Y, Lu B, Li K, Peng JY, Yi CQ. (2023) Quantitative profiling of pseudouridylation landscape in the human transcriptome. Nat. Chem. Biol., 19: 1185-1195.
Li K, Peng JY, Yi CQ. (2023) Sequencing methods and functional decoding of mRNA modifications. Fundamental Res., 3: 738-748.
Huang HL, Yi CQ, Qian PX, Weng HY, Chen JJ. (2023) Editorial: Novel insights in RNA modifications: From basic to translational research. Front. Cell. Dev. Biol., 11: 1155993.
Suzuki T, Yi CQ, Song JH. (2023) Wolf Prize in Chemistry 2023: A celebration for chemical biology. ACS Chem. Biol., 18: 671-673.
Lei ZX, Meng HW, Zhuang Y, Zhu QG, Yi CQ. (2023) Chemical and biological approaches to interrogate off-target effects of genome editing tools. ACS Chem. Biol., 18: 205-217.
Rao XC, Zhao HA, Shao CY, Yi CQ. (2023) Characterizing off-target effects of genome editors. Curr. Opin. Biomed. Eng., 28: 100480.
Chen L, Zhu BY, Ru GM, Meng, HW, Yan YC, Hong MJ, Zhang D, Luan CM, Zhang S, Wu H, Gao HY, Bai SJ, Li CQ, Ding RY, Xue NN, Lei ZX, Chen YT, Guan YT, Siwko S, Cheng YY, Song GJ, Wang LR, Yi CQ, Liu MY, Li DL. (2023) Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing. Nat. Biotechnol., 41: 663-672.
Chen L, Zhang S, Xue NN, Hong MJ, Zhang XH, Zhang D, Yang J, Bai SJ, Huang YF, Meng HW, Wu H, Luan CM, Zhu BY, Ru GM, Gao HY, Zhong LP, Liu MZ, Liu MY, Cheng YY, Yi CQ, Wang LR, Zhao YX, Song GJ, Li DL. (2023) Engineering a precise adenine base editor with minimal bystander editing. Nat. Chem. Biol., 19: 101-110.
Guo MY, Xiong MY, Peng JY, Guan T, Su HX, Huang YY, Yang CG, Li Y, Boraschi D, Pillaiyar T, Wang GB, Yi CQ, Xu YC, Chen CY. (2023) Multi-omics for COVID-19: driving development of therapeutics and vaccines. Natl. Sci. Rev., 10: nwad161.
Wang YQ, Zhang ZZ, He HQ, Song JH, Cui Y, Chen YN, Zhuang Y, Zhang XT, Li M, Zhang XX, Zhang MQ, Shi ML, Yi CQ, Wang JW. (2023) Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells. Haematologica, 108: 2677-2689.
Li XL, Yan ZY, Zhang ML, Wang JY, Xin PY, Cheng SJ, Kou LQ, Zhang XT, Wu SL, Chu JF, Yi CQ, Ye KQ, Wang B, Li JY. (2023) SnoRNP is essential for thermospermine-mediated development inArabidopsis thaliana. Sci. China-Life Sci., 66: 2-11.
Li YJ, Huang J, Bao LJ, Zhu JY, Duan WJ, Zheng HN, Wang H, Jiang YP, Liu WW, Zhang ML, Yu Y, Yi CQ, Ji X. (2023) RNA Pol II preferentially regulates ribosomal protein expression by trapping disassociated subunits. Mol. Cell., 83: 1280-1297.
Lu B, Yi CQ. (2023) TRACE-seq: Rapid, Low-Input, One-Tube RNA-seq Library Construction Based on Tagmentation of RNA/DNA Hybrids. Curr. Protoc., 3: e735.
Zhang ML, Xiao Y, Jiang Z, Yi CQ. (2023) Quantifying m6A and Ψ modifications in the transcriptome via chemical-assisted approaches. Acc. Chem. Res., 56: 2980-2991.
Lei ZX, Meng HW, Liu LL, Zhao HN, Rao XC, Yan YC, Wu H, Liu M, He AB, Yi CQ. (2022) Mitochondrial base editor induces substantial nuclear off-target mutations. Nature, 606: 804-811.
Zhuang Y, Liu JL, Wu H, Zhu QG, Yan YC, Meng HW, Chen PR, Yi CQ. (2022) Increasing the efficiency and precision of prime editing with guide RNA pairs. Nat. Chem. Biol., 18: 29-37.
Zhang ML, Sun HX, Li K, Xiao Y, Yi CQ. (2022) m6Am RNA modificationdetection by m6Am-seq. Methods., 203:242-248.
Cerneckis J, Cui Q, He C, Yi CQ, Shi YH. (2022) Decoding pseudouridine: an emerging target for therapeutic development. Trends Pharmacol. Sci., 43: 522-535.
Zhuo W, Sun M, Wang K, Zhang L, Li K, Yi DY, Li MJ, Sun Q, Ma XX, Liu W, Teng LS, Yi CQ, Zhou TH. (2022) m6Am methyltransferase PCIF1 is essential for aggressiveness of gastric cancer cells by inhibiting TM9SF1 mRNA translation. Cell Discov., 8: 48.
Liu YB, Zhou J, Li XY, Zhang XT, Shi JT, Wang XF, Li H, Miao S, Chen HF, He XX, Dong LT, Lee GR, Zheng JK, Liu RJ, Su B, Ye YQ, Flavell RA, Yi CQ, Wu, YZ, Li HB (2022). tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis.Nat. Immunol., 23: 1433-1444.
Liu Y, Li K, Xu YP, Zhu Z, Zhao H, Li XF, Ye Q, Yi CQ, Qin CF. (2022) Characterization of m6A modifications in the contemporary Zika virus genome and host cellular transcripts. J. Med. Virol.,94: 4309-4318.
Shen Y, Ou JP, He B, Yang JM, Liu HH, Wang LH, Wang BJ, Gao L, Yi CQ, Peng JY, Cen XA. (2022) 5-Hydroxymethylation alterations in cell-free DNA reflect molecular distinctions of diffuse large B cell lymphoma at different primary sites. Clin. Epigenetics, 14: 126.
Xiao M, Lu B, Ding R, Liu X, Wu X, Li YQ Liu XD, Qiu L, Zhang ZB, Xie J, Chen Y, Zhang D, Dong LT, Zhang ML, Peng JY, Yang H, Kudihna T, Xu YC, Li TS, Yi CQ, Zhu L. (2022) Metatranscriptomic analysis of host response and vaginal microbiome of patients with severe COVID-19. Sci. China-Life Sci., 65: 1473-1476.
Wu Y, Xu XC, Qi MJ, Chen C, Li MY, Yan RS, Kou XC, Zhao YH, Liu WQ, Li YH, Liu XL, Zhang ML, Yi CQ, Liu HB, Xiang JH, Wang H, Shen B, Gao YW, Gao SR. (2022) N6-methyladenosine regulates maternal RNA maintenance in oocytes and timely RNA decay during mouse maternal-to-zygotic transition. Nat. Cell Biol., 24: 917-927.
Lei ZX, Meng HW, Lv ZC, Liu MH, Zhao HN, Wu H, Zhang XX, Liu LL, Zhuang Y, Yin KL, Yan YC, Yi CQ. (2021) Detect-seq reveals out-of-protospacer editing and target-strand editing by cytosine base editors. Nat. Methods, 18: 643-651.
Liu JE, Xu YP, Li K, Ye Q, Zhou HY, Sun HX, Li XY, Yu L, Deng YQ, Li RT, Cheng ML, He B, Zhou J, Li XF, Wu AP, Yi CQ, Qin CF. (2021) The m6A methylome of SARS-CoV-2 in host cells. Cell Res., 31: 404-414.
Wang YY, Wang J, Li XY, Xiong XS, Wang JY, Zhou ZH, Zhu XX, Gu Y, Dominissini D, He L, Tian Y, Yi CQ, Fan ZS. (2021) N-1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism. Nat. Commun., 12: 6314.
Sun HX, Li K, Zhang XT, Liu JE, Zhang ML, Meng HW, Yi CQ. (2021) m6Am-seq reveals the dynamic m(6)Am methylation in the human transcriptome. Nat. Commun., 12: 4778.
He B, Zhang C, Zhang XX, Fan Y, Zeng H, Liu JE, Meng HW, Bai DS, Peng JY, Zhang Q, Tao W, Yi CQ. (2021) Tissue-specific 5-hydroxymethylcytosine landscape of the human genome. Nat. Commun., 12: 4249.
Liu MG, Zhang J, Zhu CX, Zhang XX, Xiao WD, Yan YC, Liu LL, Zeng H, Gao YQ, Yi CQ. (2021) DNA repair glycosylase hNEIL1 triages damaged bases via competing interaction modes. Nat. Commun., 12: 4108.
Lu B, Yan Y, Dong LT, Han LL, Liu YW, Yu JP, Chen JJ, Yi DY, Zhang ML, Deng X, Wang C, Wang RK, Wang DP, Wei HP, Liu D, Yi CQ. (2021) Integrated characterization of SARS-CoV-2 genome, microbiome, antibiotic resistance and host response from single throat swabs. Cell Discov., 7: 19.
Cui Q, Yin KL, Zhang XT, Ye P, Chen XW, Chao JF, Meng HW, Wei JB, Roeth D, Li L, Qin Y, Sun GH, Zhang MZ, Klein J, Huynhle M, Wang C, Zhang LY, Badie B, Kalkum M, He CA, Yi CQ, Shi YH. (2021) Targeting PUS7 suppresses tRNA pseudouridylation and glioblastoma tumorigenesis. Nat. Cancer, 2: 932-949.
Bai DS, Peng JY, Yi CQ. (2021) Advances in single-cell multi-omics profiling. RSC Chem. Biol., 2: 441-449.
Li XY, Peng JY, Yi CQ. (2021) The epitranscriptome of small non-coding RNAs. Noncoding RNA Res. 6:167-173.
Wang K, Peng JY, Yi CQ. (2021) The m6A Consensus Motif Provides a Paradigm of Epitranscriptomic Studies. Biochemistry., 60: 3410-3412.
Liu JE, Li K, Cai JB, Zhang MC, Zhang XT, Xiong XS, Meng HW, Xu XZ, Huang ZB, Peng JY, Fan J, Yi CQ. (2020) Landscape and regulation of m(6)A and m(6)Am methylome across human and mouse tissues. Mol. Cell, 77: 426-440.
Lu B, Dong LT, Yi DY, Zhang ML, Zhu CX, Li XY, Yi CQ. (2020) Transposase-assisted tagmentation of RNA/DNA hybrid duplexes. eLife, 9: e54919.
Song JH, Zhuang Y, Zhu CX, Meng HW, Lu B, Xie BT, Peng JY, Li M, Yi CQ. (2020) Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation. Nat. Chem. Biol., 16: 160-169.
Liu LL, Zhang Y, Liu MH, Wei WS, Yi CQ, Peng JY. (2020) Structural insights into the specific recognition of 5-methylcytosine and 5-hydroxymethylcytosine by TAL effectors. J. Mol. Biol., 432: 1035-1047.
Zhao LY, Song JH, Liu YB, Song CX, Yi CQ. (2020) Mapping the epigenetic modifications of DNA and RNA. Protein Cell., 11: 792-808.
Li XY, Yi CQ. (2020) A novel epigenetic mark derived from vitamin C. Biochem., 59: 8-9.
Song JH, Yi CQ. (2020) Reading chemical modifications in the transcriptome. J. Mol. Biol.,432: 1824-1839.
Li X, Liang QX, Lin JR, Peng JY, Yang JH, Yi CQ, Yu Y, Zhang QC, Zhou KR. (2020) Epitranscriptomic technologies and analyses. Sci. China Life Sci., 63: 501-515.
Jinying Peng, Haowei Meng, Bo Lu, Bo He, Qiang Huang, Yongtai Bai, Yuan Zhuang, Hanxiao Sun, Xueqing Yan, Zhe Zhou, Xin Li, Xiaoting Zhang, Jinmin Yang, Jiangle Liu, Huannan Zhao, Yongchang Yan, Hao Wu, Nan Luo, Ye Xiao, Xichen Rao, Chuyun Shao, Liqiong Ou, Wenqing Liu, Qingguo Zhu, Yichen Ma, Yixuan Lin, Xiangyue Shen, Ruoqi Lin, Mingyang Li, Puzhe Geng, Sihan Zhang, Yujia Liu, Yuhao Zhang, Haoning Zhang, Mengzhu Gao
