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情况简介
院士风采
杰出青年
全所PI名录
 
 
地址:上海市岳阳路320号
邮编:200031
电话:86-21-54920000
传真:86-21-54921011
邮箱:sibcb@sibcb.ac.cn

全所PI名录 >

 
惠静毅
研究员,研究组长,博士生导师
E-mail: jyhui@@sibcb.ac.cn


个人简介

        1993年复旦大学微生物系毕业,获学士学位。
        1999年德国Free University Berlin毕业,获硕士学位。
        2003年德国Justus-Liebig-University Giessen毕业,获博士学位。
        2008年回国后,任中科院上海生科院生化与细胞所研究员,研究组长。


研究方向

RNA加工的调控与功能


研究工作
        RNA加工 (RNA processing)是RNA成熟并发挥功能所必不可少的步骤,也是基因表达过程中的一个重要调控层面。我们实验室主要关注调控mRNA与非编码RNA加工成熟的分子机制,并探索在人类疾病中这些机制是如何失调的。
        在高等真核生物中,大多数蛋白编码基因含有外显子(exon)和内含子(intron)顺序。通常,内含子通过mRNA剪接(splicing)的过程从mRNA前体(pre-mRNA)中被准确而有效地去除;外显子则被连接成为成熟的mRNA。然而,通过可变剪接(alternative splicing),一个mRNA前体可以生成多种mRNA异构体(isoforms)。它们往往能够编码具有不同、甚至带有拮抗功能的蛋白质。2008年,高通量测序的结果显示94%的人类基因至少发生一次可变剪接事件。可变剪接具有组织、发育阶段及疾病进程特异性,并且受外界刺激地调控。因此,可变剪接是一个能够产生蛋白多样性及调控基因表达的重要机制。剪接异常与许多疾病密切相关。我们采用生物化学、分子生物学、细胞生物学及生物信息学的手段探索RNA和蛋白质相互作用决定剪接位点选择的分子机制;信号转导途径调控可变剪接的机制;以及可变剪接在肿瘤发生发展中的功能。
        细胞含有许多非编码RNA,包括基因表达机器中的主要成分snRNA、tRNA、rRNA等以及其它许多长短不同的调控RNA。miRNA是一类长约22 nt的小分子非编码调控RNA。它们通过调节mRNA稳定性和蛋白翻译的方式影响基因表达。miRNA的表达水平受到严格地时空控制,并在个体发育和细胞增殖、分化、代谢及凋亡等过程中发挥重要功能。我们主要关注miRNA自身的生物合成是如何受到调控的以及这些调控在干细胞命运决定中的功能是什么。


代表性论文

  1. Müller-McNicoll M, Rossbach O, Hui J, Medenbach J.Auto-regulatory feedback by RNA-binding proteins.J Mol Cell Biol,2019, pii: mjz043
  2. Yang XJ, Zhu H, Mu SR, Wei WJ, Yuan X, Wang M, Liu Y, Hui J#, Huang Y#.Crystal structure of a Y-box binding protein 1 (YB-1)-RNA complex reveals key features and residues interacting with RNA. J Biol Chem, 2019, pii: jbc.RA119.007545
  3. Wu DR, Gu KL, Yu JC, Fu X, Wang XW, Guo WT, Liao LQ, Zhu H, Zhang XS, Hui J*, Wang Y*. Opposing roles of miR-294 and MBNL1/2 in shaping the gene regulatory network of embryonic stem cells. EMBO Rep. 2018;19(6). pii: e45657.
  4. Wang F, Fu X, Chen P, Wu P, Fan XJ, Li N, Zhu H, Jia Ting-Ting, Ji HB, Wang ZF, Wong C. C L, Hu RG#, Hui J#. SPSB1-mediated HnRNP A1 ubiquitylation regulates alternative splicing and cell migration in EGF signaling. (2017) Cell Res, doi: 10.1038/cr.2017.7 (highlighted by Fu XD, Cell Research, 2017.2.10)
  5. Wang F, Song W, Zhao HM, Ma YN, Li YX, Zhai D, Pi JN, Si YM, Xu JY, Dong L, Su R, Zhang MM, Zhu Y, Ren XX, Miao F, Liu WJ, Li FJ, Zhang JW, He AB, Shan G, Hui J, Wang LF, Yu J. The RNA-binding protein QKI5 regulates primary miR-124-1 processing via a distal RNA motif during erythropoiesis, (2017) Cell Res, doi: 10.1038/cr.2017.26
  6. Li F, Yi P, Pi J, Li L, Hui J, Wang F, Liang A, Yu J.QKI5-mediated alternative splicing of the histone variant macroH2A1 regulates gastric carcinogenesis. (2016) Oncotarget, 7, 32821-32834
  7. Wu SL, Fu X, Huang J, Jia TT, Zong FY, Mu SR, Zhu H, Yan Y, Qiu S, Wu Q, Yan W, Peng Y, Chen J, Hui J#. Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme. (2015) Nucleic Acids Res, 43, 8516-8528
  8. Guo R, Zheng L, Park JW, Lv R, Chen H, Jiao F, Xu W, Mu S, Wen H, Qiu J, Wang Z, Yang P, Wu F, Hui J, Fu X, Shi X, Shi YG, Xing Y, Lan F, Shi Y. BS69/ZMYND11 reads and connects histone H3.3 lysine 36 trimethylation-decorated chromatin to regulated pre-mRNA processing. (2014) Mol Cell, 56, 298-310
  9. Zong FY, Fu X, Wei WJ, Luo YG, Heiner M, Cao LJ, Fang Z, Fang R, Lu D, Ji H, Hui J#. The RNA-binding protein QKI suppresses cancer-associated aberrant splicing. (2014) PLOS Genet, 10, e1004289
  10. Jiang Y, Hui J#. Chromatin structure and mRNA alternative splicing. (2014) Chem Life, 4, 449-455 (invited review)
  11. Wei WJ, Mu SR, Heiner M, Fu X, Cao LJ, Gong XF, Bindereif A, Hui J#. YB-1 binds to CAUC motifs and stimulates exon inclusion by enhancing the recruitment of U2AF to weak polypyrimidine tracts. (2012) Nucleic Acids Res, 40, 8622-8636
  12. Huang Y, Li W, Yao X, Lin QJ, Yin JW, Liang Y, Heiner M, Tian B, Hui J, Wang G. Mediator complex regulates alternative mRNA processing via the MED23 subunit. (2012) Mol Cell, 45, 459-469
  13. Heiner M, Hui J, Schreiner S, Hung LH, Bindereif A. HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition. (2010) RNA Biol, 7, 56-64
  14. Kishore S, Khanna A, Zhang Z, Hui J, Balwierz PJ, Stefan M, Beach C, Nicholls RD, Zavolan M, Stamm S. The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing. (2010) Hum Mol Genet, 19, 1153-1164
  15. Roßbach O, Hung LH, Schreiner S, Grishina I, Heiner M, Hui J, Bindereif A. Auto- and crossregulation of the hnRNP L proteins by alternative splicing. (2009) Mol Cell Biol, 29, 1442-1451
  16. Hui J. Regulation of mammalian pre-mRNA splicing. (2009) Sci China C Life Sci, 52, 253-260 (invited review)
  17. Hui J, Kishore S, Khanna A, Stamm S. Analysis of alternative splicing with microarrays. (2009) In Bioinformatics for Systems Biology (Krawetz SA ed.), Humana Press, pp267-279
  18. Hung LH*, Heiner M*, Hui J*, Schreiner S, Benes V, Bindereif A. Diverse roles of hnRNP L in mammalian mRNA processing: a combined microarray and RNAi analysis. (2008) RNA, 14, 284-296
  19. Lorenz M, Hewing B, Hui J, Zepp A, Baumann G, Bindereif A, Stangl V, Stangl K. Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity. (2007) FASEB J, 21, 1556-1564
  20. Hui J, Bindereif A. Alternative pre-mRNA splicing in the human system: unexpected role of repetitive sequences as regulatory elements. (2005) Biol Chem, 386, 1265-1271 (invited review)
  21. Hui J*, Hung LH*, Heiner M, Schreiner S, Neumuller N, Reither G, Haas SA, Bindereif A. Intronic CA-repeat and CA-rich elements: a new class of regulators of mammalian alternative splicing. (2005) EMBO J, 24, 1988-1998
  22. Palfi Z, Hui J, Bindereif A. Biotin-based affinity purification of RNA-protein complexes. (2004) In Handbook of RNA biochemistry, (Westhof E, Bindereif A, Schön A, Hartmann RK eds), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp676-693
  23. Hui J, Reither G, Bindereif A. Novel function role of CA repeats and hnRNP L in RNA stability. (2003) RNA, 9, 931-936
  24. Hui J, Stangl K, Lane WL, Bindereif A. HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats. (2003) Nat Struct Biol, 10, 33-37. Comment by Bilbao D, Valcárcel J. Getting to the heart of a splicing enhancer. (2003) Nat Struct Biol, 10, 6-7
  25. Yang J, Hui J, Li G, Wang Y, Yuan H, Li Y. Expression of the recombinant hepatitis B virus surface antigen carrying preS epitopes in Pichia pastoris. (2000) Acta Biochimica et Biophysica Sinica, 32, 39-144
  26. Hui J, Li G, Kong Y, Wang Y. Expression and characterization of chimeric hepatitis B surface antigen particles carrying preS epitopes. (1999) J Biotechnol, 72, 49-59
  27. Hui J, Mancini M, Li G, Wang Y, Tiollais P, Michel ML. (1999) Immunization with a plasmid encoding a modified hepatitis B surface antigen carrying the receptor binding site for hepatocytes. Vaccine, 17, 1711-1718
  28. Hui J, Li G, Kong Y, Wang Y. DNA-mediated immunization against hepatitis B surface antigen carrying preS epitopes. (1999)Chinese Science Bulletin, 44, 620-623
  29. Hui J, Li G, Kong Y, Wang Y. A modified HBsAg containing the preS1 and preS2 epitopes. (1998) Sci China C Life Sci, 41, 56-63

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