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人才隊(duì)伍

周小龍
研究員，研究組長(zhǎng),博士生導(dǎo)師
E-mail: xlzhou@sibcb.ac.cn
實(shí)驗(yàn)室主頁(yè):

個(gè)人簡(jiǎn)介：

　　2004年7月畢業(yè)于安徽師范大學(xué)生命科學(xué)學(xué)院，獲得理學(xué)學(xué)士學(xué)位;2009年5月畢業(yè)于中國(guó)科學(xué)院上海生命科學(xué)研究院，獲得理學(xué)博士學(xué)位。2009年6月至2017年10月，任中科院生化與細(xì)胞所助理研究員、副研究員;2009年11月至2010年1月，法國(guó)國(guó)家科研中心(CNRS)斯特拉斯堡分子與細(xì)胞生物學(xué)研究所訪問(wèn)學(xué)者;2010年7月至2010年12月，美國(guó)耶魯大學(xué)分子生物物理與生物化學(xué)系訪問(wèn)學(xué)者;2017年11月起任生化與細(xì)胞所研究員;2019年5月起，任生化與細(xì)胞所研究組長(zhǎng)、博士生導(dǎo)師。榮獲2011年度中科院盧嘉錫青年人才獎(jiǎng)、中科院青年創(chuàng)新促進(jìn)會(huì)會(huì)員、2012年度賽諾菲-中科院上海生科院優(yōu)秀青年人才獎(jiǎng)、2015年度中科院青年創(chuàng)新促進(jìn)會(huì)優(yōu)秀會(huì)員、2016年度上海市青年科技啟明星、2018年度國(guó)家自然科學(xué)基金優(yōu)秀青年基金等人才項(xiàng)目或稱號(hào)。

社會(huì)任職：

研究方向：

RNA代謝與線粒體疾病

研究工作：

　　RNA是遺傳信息傳遞中最為關(guān)鍵的生物大分子之一。RNA被轉(zhuǎn)錄后，需要經(jīng)歷加工、修飾、成熟、降解等一系列代謝過(guò)程。這些RNA代謝過(guò)程對(duì)于正常生命活動(dòng)具有重要的生物學(xué)意義。在已發(fā)現(xiàn)的170多種RNA表觀遺傳修飾中，絕大多數(shù)(>120種)發(fā)生在tRNA分子上。tRNA轉(zhuǎn)錄后表觀遺傳修飾種類最多，機(jī)制最為多樣與復(fù)雜。tRNA修飾由tRNA修飾酶介導(dǎo)，決定tRNA結(jié)構(gòu)、穩(wěn)定性、遺傳信息傳遞的速度與精確性、蛋白質(zhì)穩(wěn)態(tài)維持等。成熟的tRNA在細(xì)胞質(zhì)或線粒體氨基酰-tRNA合成酶介導(dǎo)的氨基?；c編校反應(yīng)的催化下連接上正確的氨基酸，參與蛋白質(zhì)合成。
　　人細(xì)胞具有兩套遺傳物質(zhì)：核基因組和線粒體基因組。線粒體是真核細(xì)胞關(guān)鍵細(xì)胞器，其蛋白質(zhì)組由兩套遺傳物質(zhì)共同編碼。線粒體基因組只編碼37個(gè)基因，產(chǎn)生氧化呼吸鏈復(fù)合物關(guān)鍵的13種跨膜蛋白質(zhì)，對(duì)于氧化呼吸鏈復(fù)合物正確組裝與行使功能至關(guān)重要。線粒體相關(guān)的核基因(包括線粒體氨基酰-tRNA合成酶、tRNA修飾酶等)以及線粒體自身基因(包括線粒體tRNA)遺傳變異主要影響中樞/外周神經(jīng)、心臟、肌肉、內(nèi)分泌等系統(tǒng)，導(dǎo)致線粒體功能異常，造成人類疾病，統(tǒng)稱為線粒體疾病(例如腦白質(zhì)病、認(rèn)知障礙、心臟病、肌無(wú)力、腎衰、癲癇等)。
　　研究組運(yùn)用生物化學(xué)、分子生物學(xué)、細(xì)胞生物學(xué)、遺傳學(xué)等技術(shù)方法，主要研究：(1) tRNA、氨基酰-tRNA合成酶與tRNA修飾酶介導(dǎo)的人細(xì)胞質(zhì)與線粒體蛋白質(zhì)合成的分子機(jī)制;(2)闡明臨床發(fā)生的蛋白質(zhì)合成缺陷相關(guān)線粒體疾病的致病機(jī)制;(3)探索線粒體疾病靶向診斷與干預(yù)策略。

承擔(dān)科研項(xiàng)目情況：

代表論著：

1. Liu N^#, Liu B^#, Ma CR^#, Cai Z, Wang JT, Chai ZQ, Zhu N, Shao T, Chen YL, Lin Y*, Wang Y*, Xu H*, Zhou XL*, Mammalian tRNA acetylation determines translation efficiency and tRNA quality control. Nat. Commun., 2025, 16(1):5496.
2. Yao SY, Zhou XL*, Tangled but ordered human mitochondrial tRNA maturation. SCIENCE CHINA Life Sciences. 2025, doi: 10.1007/s11427-024-2782-1.
3. Lu JL^#, Dai Y^#, Ji K^#, Peng GX, Li H, Yan C*, Shen B*, Zhou XL*, Taurine hypomodification underlies mitochondrial tRNA^Trp-related genetic diseases. Nucleic Acids Res., 2024, 52(21):13351-13367.
4. 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.
5. 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.
6. 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.
7. Zhang JH, Eriani G*, Zhou XL*, Pathophysiology of human mitochondrial tRNA metabolism. Trends Endocrinol. Metab., 2024, 35(4): 285-289.
8. 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.
9. 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 tRNA^Thr mischarged with alanine. Int. J. Biol. Macromol., 2023, 253, 127121.
10. 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.
11. 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.
12. 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 UPR^mt. Redox Biology, 2023, 63, 102722
13. 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.
14. 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
15. 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.
16. 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 tRNA^Ser(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease. Nucleic Acids Res., 2022, 50(20):11755-11774.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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. ?
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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 tRNA^Lys. Sci. China Life Sci., 2020, 63(8):1227-1239.
30. 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.
31. 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.
32. Wang Y, Zeng QY, Zheng WQ, Ji QQ, Zhou XL*, Wang ED*. A natural non-Watson-Crick base pair in human mitochondrial tRNA^Thr causes structural and functional susceptibility to local mutations. Nucleic Acids Res., 2018, 46(9), 4662-4676.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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 tRNA^Ser and tRNA^Leu. J. Biol. Chem., 2016, 291(7):3613-3625.
39. 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.
40. 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.
41. 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.
42. 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 tRNA^Leu in the archaeal mode. Nucleic Acids Res., 2014, 42(8):5109-5124.
43. 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)
44. 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.
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. 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.
51. 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.
52. Zhou XL and Wang ED*, Mitochondrial aminoacyl-tRNA synthetases related to human diseases. Prog. Biochem. Biophys., 2008, 35(8):853-858. (Review)

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個(gè)人簡(jiǎn)介：

社會(huì)任職：

研究方向：

研究工作：

承擔(dān)科研項(xiàng)目情況：

代表論著：

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研究組成員：