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  • 周小龙
  • 研究员，研究组长,博士生导师
  • E-mail: xlzhou@sibcb.ac.cn
  • 实验室主页: 
    个人简介：

  • 　　2004年7月毕业于安徽师范大学生命科学学院，获得理学学士学位;2009年5月毕业于中国科学院上海生命科学研究院，获得理学博士学位。2009年6月至2017年10月，任中科院生化与细胞所助理研究员、副研究员;2009年11月至2010年1月，法国国家科研中心(CNRS)斯特拉斯堡分子与细胞生物学研究所访问学者;2010年7月至2010年12月，美国耶鲁大学分子生物物理与生物化学系访问学者;2017年11月起任生化与细胞所研究员;2019年5月起，任生化与细胞所研究组长、博士生导师。荣获2011年度中科院卢嘉锡青年人才奖、中科院青年创新促进会会员、2012年度赛诺菲-中科院上海生科院优秀青年人才奖、2015年度中科院青年创新促进会优秀会员、2016年度上海市青年科技启明星、2018年度国家自然科学基金优秀青年基金等人才项目或称号。

    社会任职：
    研究方向：
  • RNA代谢与线粒体疾病
    研究工作：

  • 　　RNA是遗传信息传递中最为关键的生物大分子之一。RNA被转录后，需要经历加工、修饰、成熟、降解等一系列代谢过程。这些RNA代谢过程对于正常生命活动具有重要的生物学意义。在已发现的170多种RNA表观遗传修饰中，绝大多数(>120种)发生在tRNA分子上。tRNA转录后表观遗传修饰种类最多，机制最为多样与复杂。tRNA修饰由tRNA修饰酶介导，决定tRNA结构、稳定性、遗传信息传递的速度与精确性、蛋白质稳态维持等。成熟的tRNA在细胞质或线粒体氨基酰-tRNA合成酶介导的氨基酰化与编校反应的催化下连接上正确的氨基酸，参与蛋白质合成。

    　　人细胞具有两套遗传物质：核基因组和线粒体基因组。线粒体是真核细胞关键细胞器，其蛋白质组由两套遗传物质共同编码。线粒体基因组只编码37个基因，产生氧化呼吸链复合物关键的13种跨膜蛋白质，对于氧化呼吸链复合物正确组装与行使功能至关重要。线粒体相关的核基因(包括线粒体氨基酰-tRNA合成酶、tRNA修饰酶等)以及线粒体自身基因(包括线粒体tRNA)遗传变异主要影响中枢/外周神经、心脏、肌肉、内分泌等系统，导致线粒体功能异常，造成人类疾病，统称为线粒体疾病(例如脑白质病、认知障碍、心脏病、肌无力、肾衰、癫痫等)。

    　　研究组运用生物化学、分子生物学、细胞生物学、遗传学等技术方法，主要研究：(1) tRNA、氨基酰-tRNA合成酶与tRNA修饰酶介导的人细胞质与线粒体蛋白质合成的分子机制;(2)阐明临床发生的蛋白质合成缺陷相关线粒体疾病的致病机制;(3)探索线粒体疾病靶向诊断与干预策略。

    承担科研项目情况：
    代表论著：
    1. Lu JL#, Dai Y#, Ji K#, Peng GX, Li H, Yan C*, Shen B*, Zhou XL*, Taurine hypomodification underlies mitochondrial tRNATrp-related genetic diseases. Nucleic Acids Res., 2024, DOI: 10.1093/nar/gkae854.
    2. Mao XL, Eriani G, Zhou XL*, ADATs: Roles in tRNA editing and relevance to disease. Acta Biochim. Biophys. Sin., 2024, doi.org/10.3724/abbs.2024125.
    3. Li ZH, Zhou XL*, Eukaryotic AlaX provides multiple checkpoints for quality and quantity of aminoacyl-tRNAs in translation. Nucleic Acids Res., 2024, 52(13): 7825-7842.
    4. Ma CR, Liu N, Li H, Xu H, Zhou XL*, Activity reconstitution of Kre33 and Tan1 reveals a molecular ruler mechanism in eukaryotic tRNA acetylation. Nucleic Acids Res., 2024, 52(9): 5226-5240.
    5. Zhang JH, Eriani G*, Zhou XL*, Pathophysiology of human mitochondrial tRNA metabolism. Trends Endocrinol. Metab., 2024, 35(4): 285-289.
    6. Zhang Y#, Zhou JB#, Yin Y, Wang ED*, Zhou XL*, Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. Nucleic Acids Res., 2024, 52(6):3213-3233.
    7. Yuan C#, Li ZH#, Luo X, Huang P, Guo L, Lu M, Xia J, Xiao Y*, Zhou XL*, Chen M*, Mammalian trans-editing factor ProX is able to deacylate tRNAThr mischarged with alanine. Int. J. Biol. Macromol., 2023, 253, 127121.
    8. Zheng WQ, Zhang JH, Li ZH, Liu X, Zhang Y, Huang S, Li J, Zhou B, Eriani G, Wang ED*, Zhou XL*, Mammalian mitochondrial translation infidelity leads to oxidative stress-induced cell cycle arrest and cardiomyopathy. Proc. Natl. Acad. Sci. USA, 2023, 120(37), e2309714120.
    9. Huang MH, Wang JT, Zhang JH, Mao XL, Peng GX, Lin X, Lv D, Yuan C, Lin H, Wang ED*, Zhou XL*, Mitochondrial RNA m3C methyltransferase METTL8 relies on an isoform-specific N-terminal extension and modifies multiple heterogenous tRNAs. Science Bulletin, 2023, 68(18): 2094-2105.
    10. Guo M#, Qiao X#, Wang Y#, Li ZH#, Shi C, Chen Y, Kang L, Chen C*, Zhou XL*, Mitochondrial translational defect extends lifespan in C. elegans by activating UPRmt. Redox Biology, 2023, 63, 102722
    11. Lu JL, Zhou XL*, SARS-CoV-2 main protease Nsp5 cleaves and inactivates human tRNA methyltransferase TRMT1. J. Mol. Cell Biol., 2023, 15(4), mjad024.
    12. Zeng QY#, Zhang F#, Zhang JH#, Hei Z#, Li ZH, Huang MH, Fang P*, Wang ED*, Sun XJ*, Zhou XL*, Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development. J. Biol. Chem., 2023, 299(5): 104704
    13. Peng GX#, Mao XL#, Cao YT, Yao SY, Li QR, Chen X, Wang ED*, Zhou XL*, RNA granule-clustered mitochondrial aminoacyl-tRNA synthetases form multiple complexes with the potential to fine-tune tRNA aminoacylation. Nucleic Acids Res., 2022, 50(22): 12951-12968.
    14. Yu T#, Zhang Y#, Zheng WQ, Wu S, Li G, Zhang Y, Li N, Yao R, Fang P, Wang J*, Zhou XL*, Selective degradation of tRNASer(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease. Nucleic Acids Res., 2022, 50(20):11755-11774.
    15. Huang MH, Peng GX, Mao XL, Wang JT, Zhou JB, Zhang JH, Chen M, Wang ED*, Zhou XL*. Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8. Nucleic Acids Res., 2022, 50(7):4012-4028.
    16. Wu S, Zheng L, Hei Z, Zhou JB, Li G, Li P, Wang J, Ali H, Zhou XL, Wang J, Fang P. Human lysyl-tRNA synthetase evolves a dynamic structure that can be stabilized by forming complex. Cell. Mol. Life Sci., 2022, 79(2):128.
    17. Wang JT#, Zhou JB#, Mao XL, Zhou L, Chen M, Zhang W, Wang ED*, Zhou XL*. Commonality and diversity in tRNA substrate recognition in t6A biogenesis by eukaryotic KEOPSs. Nucleic Acids Res., 2022, 50(4):2223-2239.
    18. Zheng WQ, Pedersen SV, Thompson K, Bellacchio E, French CE, Munro B, Pearson TS, Vogt J, Diodato D, Diemer T, Ernst A, Horvath R, Chitre M, Ek J, Wibrand F, Grange DK, Raymond L, Zhou XL*, Taylor RW, Ostergaard E*. Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease, Hum Mol Genet., 2022, 31(4):523-534.
    19. Chen R, Zhou J, Liu L, Mao XL, Zhou XL, Xie W. Crystal structure of human METTL6, the m3C methyltransferase. Commun. Biol., 2021, 4(1):1361.
    20. Zhou JB, Wang ED*, Zhou XL*. Modifications of the human tRNA anticodon loop and their associations with genetic diseases. Cell. Mol. Life Sci., 2021, 78(23):7087-7105.
    21. Zhang F#, Zeng QY#, Xu H#, Xu A#, Liu DJ, Li NZ, Chen Y, Jin Y, Xu CH, Feng CZ, Zhang YL, Liu D, Liu N, Xie Y, Yu SH, Yuan H, Xue K, Shi JY, Liu T, Xu PF, Zhao WL, Zhou Y, Wang L, Huang QH, Chen Z, Chen SJ*, Zhou XL*, Sun XJ*. Selective and competitive functions of the AAR and UPR pathways in stress-induced angiogenesis. Cell Discovery, 2021, 7(1):98.  
    22. Mao XL, Li ZH, Huang MH, Wang JT, Zhou JB, Li QR, Xu H, Wang XJ, Zhou XL*. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. Nucleic Acids Res., 2021, 49(14): 8309-8323.
    23. Peng GX, Zhang Y, Wang QQ, Li QR, Xu H, Wang ED*, Zhou XL*. The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases. Nucleic Acids Res., 2021, 49(5): 2816–2834.
    24. Li G, Eriani G, Wang ED*, Zhou XL*. Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease. Sci. China Life Sci., 2021, 64(10):1645-1660.
    25. Zheng WQ#, Zhang Y#, Yao Q#, Chen Y#, Qiao XH, Wang ED*, Chen C*, Zhou XL*. Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation. Nucleic Acids Res., 2020, 48(12):6799-6810.
    26. Zhou JB, Wang Y, Zeng QY, Meng SX, Wang ED*, Zhou XL*. Molecular basis for t6A modification in human mitochondria. Nucleic Acids Res., 2020, 48(6):3181-3194.
    27. Wang Y#, Zhou JB#, Zeng QY, Wu S, Xue MQ, Fang P, Wang ED*, Zhou XL*. Hearing impairment-associated KARS mutations lead to defects in aminoacylation of both cytoplasmic and mitochondrial tRNALys. Sci. China Life Sci., 2020, 63(8):1227-1239.
    28. Zhou XL#,*, Chen Y#, Zeng QY, Ruan ZR, Fang P, Wang ED*. Newly acquired N-terminal extension targets threonyl-tRNA synthetase-like protein into the multiple tRNA synthetase complex. Nucleic Acids Res., 2019, 47(16), 8662-8674.
    29. Zeng QY, Peng GX, Li G, Zhou JB, Zheng WQ, Xue MQ, Wang ED*, Zhou XL*. The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase. Nucleic Acids Res., 2019, 47(6), 3072-3085.
    30. Wang Y, Zeng QY, Zheng WQ, Ji QQ, Zhou XL*, Wang ED*. A natural non-Watson-Crick base pair in human mitochondrial tRNAThr causes structural and functional susceptibility to local mutations. Nucleic Acids Res., 2018, 46(9), 4662-4676.
    31. Chen Y, Ruan ZR, Wang Y, Huang Q, Xue MQ, Zhou XL*, Wang ED*. A threonyl-tRNA synthetase-like protein has tRNA aminoacylation and editing activities. Nucleic Acids Res., 2018, 46(7), 3643-3656.
    32. Hilander T#, Zhou XL#, Konovalova S, Zhang FP, Euro L, Chilov D, Poutanen M, Chihade J, Wang ED*, Tyynismaa H*. Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria. Nucleic Acids Res., 2018, 46(2), 849-860.
    33. Zhou XL#, He LX#, Yu LJ#, Wang Y, Wang XJ*, Wang ED*, Yang T*. Mutations in KARS cause early-onset hearing loss and leukoencepha lopathy: Potential pathogenic mechanism. Human Mutation, 2017, 38(12):1740-1750.
    34. Zhou XL#, Chen Y#, Fang ZP, Ruan ZR, Wang Y, Liu RJ, Xue MQ, Wang ED*. Translational quality control by bacterial threonyl-tRNA synthetases. J. Biol. Chem., 2016, 291(40), 21208-21221.
    35. Wang Y#, Zhou XL#,*, Ruan ZR#, Liu RJ, Eriani G, Wang ED*. A human disease-causing point mutation in mitochondrial threonyl-tRNA synthetase induces both structural and functional defects. J. Biol. Chem., 2016, 291(12):6507-6520.
    36. Ji QQ, Fang ZP, Ye Q, Ruan ZR, Zhou XL*, Wang ED*. C-terminal domain of leucyl-tRNA synthetase from pathogenic Candida albicans recognizes both tRNASer and tRNALeu. J. Biol. Chem., 2016, 291(7):3613-3625.
    37. Ye Q, Wang M, Fang ZP, Ruan ZR, Ji QQ, Zhou XL*, Wang ED*. Degenerate CP1 domain from human mitochondrial leucyl-tRNA Synthetase. J. Biol. Chem., 2015, 290(40):24391-24402.
    38. Ruan ZR, Fang ZP, Ye Q, Lei HY, Eriani G, Zhou XL*, Wang ED*. Identification of lethal mutations in yeast threonyl-tRNA synthetase revealing critical residues in its human homolog. J. Biol. Chem., 2015, 290(3):1664-1678.
    39. Zhou XL, Ruan ZR, Wang M, Fang ZP, Wang Y, Chen Y, Liu RJ, Eriani G, Wang ED*, A minimalist mitochondrial threonyl-tRNA synthetase exhibits tRNA-isoacceptor specificity during proofreading. Nucleic Acids Res., 2014, 42(22):13873-13886.
    40. Fang ZP, Wang M, Ruan ZR, Tan M, Liu RJ, Zhou M, Zhou XL*, Wang ED*. Co-existence of bacterial leucyl-tRNA synthetases with archaeal tRNA binding domains that distinguish tRNALeu in the archaeal mode. Nucleic Acids Res., 2014, 42(8):5109-5124.
    41. Zhou XL and Wang ED*. Transfer RNA: a dancer between charging and mis-charging for protein biosynthesis. Sci. China Life Sci., 2013, 56(10):921-932. (Invited review)
    42. Zhou XL, Fang ZP, Ruan ZR, Wang M, Liu RJ, Tan M, Anella F, Wang ED*. Aminoacylation and translational quality control strategy employed by leucyl-tRNA synthetase from a human pathogen with genetic code ambiguity. Nucleic Acids Res., 2013, 41(21):9825-9838.
    43. Zhou XL, Ruan ZR, Huang Q, Tan M, Wang ED*. Translational fidelity maintenance preventing Ser mis-incorporation at Thr codon in protein from eukaryote. Nucleic Acids Res., 2013, 41(1):302-314.
    44. Zhou XL, Du DH, Tan M, Lei HY, Ruan LL, Eriani G, Wang ED*. Role of tRNA amino acid-accepting end in aminoacylation and its quality control. Nucleic Acids Res., 2011, 39(20):8857-8868.
    45. Zhou XL, Tan M, Wang M, Chen X, Wang ED*. Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690. Biochem J., 2010, 430(2):325-333.
    46. Zhou XL, Wang M, Tan M, Huang Q, Eriani G, Wang ED*. Functional characterization of leucine-specific domain 1 from eukaryal and archaeal leucyl-tRNA synthetases. Biochem J., 2010, 429(3):505-513.
    47. Zhou XL and Wang ED*. Two tyrosine residues outside the editing active site in Giardia lamblia leucyl-tRNA synthetase are essential for the post-transfer editing. Biochem. Biophys. Res. Commun., 2009, 386(3):510-515.
    48. Zhou XL, Yao P, Ruan LL, Zhu B, Luo J, Qu LH, Wang ED*. A unique peptide in the CP1 domain of Giardia lamblia leucyl-tRNA Synthetase. Biochemistry (US), 2009, 48(6):1340-1347.
    49. Zhou XL, Zhu B, Wang ED*. The CP2 domain of leucyl-tRNA synthetase is crucial for amino acid activation and post-transfer editing. J. Biol. Chem., 2008, 283(52):36608-36616.
    50. Zhou XL and Wang ED*, Mitochondrial aminoacyl-tRNA synthetases related to human diseases. Prog. Biochem. Biophys., 2008, 35(8):853-858. (Review)
    获奖及荣誉：
    研究组成员：
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