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Heng-Chi Lee

TitleAssistant Professor
InstitutionUniversity of Chicago
DepartmentMol Gen/Cell Bio
AddressChicago IL 60637
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    Small non-coding RNAs play remarkable roles in regulating gene expression by binding to Argonaute family proteins and guiding them to recognize their targets. We are interested in understanding how small RNAs function as a surveillance system that defends the genome against foreign nucleic acids, such as transposons. A conserved subfamily of Argonaute, named PIWI, binds PIWI-interacting RNA (piRNA) and plays critical roles in silencing transposons in various animals. Using C. elegans as a model organism, our recent study suggests PIWI and >25,000 genome-encoded piRNAs survey the whole transcriptome to detect "non-self" nucleic acids. Interestingly, our research demonstrated that piRNAs can establish "non-self memory" that silences its targets over multiple generations! In addition, self-transcripts appear to be protected by another group of small RNAs from piRNA silencing.

    Genetic analyses have laid the groundwork for our knowledge of this defense system, but the molecular mechanisms are still poorly understood. We aim to investigate several fundamental questions including: 1. How do piRNAs recognize their RNA targets/ 2. How are "self" and "non-self" memories established and inherited? 3. How are various small RNAs produced and specifically associated with distinct Argonaute complexes? By applying complementary approaches including genomics, genetics and biochemistry, we aim to identify important principles of small RNA-based genome defense mechanisms that are likely conserved between different animals. Importantly, as PIWI mutants exhibit fertility defects in various animals, we hope our research will provide important insights toward the molecular pathogenesis of infertility.


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    R00GM108866     (LEE, HENG-CHI)Sep 1, 2014 - Dec 31, 2018
    NIH
    Mechanism of piRNA-mediated recognition and silencing of foreign genes
    Role: Principal Investigator

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Wu WS, Brown JS, Chen TT, Chu YH, Huang WC, Tu S, Lee HC. piRTarBase: a database of piRNA targeting sites and their roles in gene regulation. Nucleic Acids Res. 2019 Jan 08; 47(D1):D181-D187. PMID: 30357353.
      View in: PubMed
    2. Wu WS, Huang WC, Brown JS, Zhang D, Song X, Chen H, Tu S, Weng Z, Lee HC. pirScan: a webserver to predict piRNA targeting sites and to avoid transgene silencing in C. elegans. Nucleic Acids Res. 2018 07 02; 46(W1):W43-W48. PMID: 29897582.
      View in: PubMed
    3. Zhang D, Tu S, Stubna M, Wu WS, Huang WC, Weng Z, Lee HC. The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes. Science. 2018 02 02; 359(6375):587-592. PMID: 29420292.
      View in: PubMed
    4. Tang W, Tu S, Lee HC, Weng Z, Mello CC. The RNase PARN-1 Trims piRNA 3' Ends to Promote Transcriptome Surveillance in C. elegans. Cell. 2016 Feb 25; 164(5):974-84. PMID: 26919432.
      View in: PubMed
    5. Gu W, Lee HC, Chaves D, Youngman EM, Pazour GJ, Conte D, Mello CC. CapSeq and CIP-TAP identify Pol II start sites and reveal capped small RNAs as C. elegans piRNA precursors. Cell. 2012 Dec 21; 151(7):1488-500. PMID: 23260138.
      View in: PubMed
    6. Lee HC, Gu W, Shirayama M, Youngman E, Conte D, Mello CC. C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell. 2012 Jul 06; 150(1):78-87. PMID: 22738724.
      View in: PubMed
    7. Shirayama M, Seth M, Lee HC, Gu W, Ishidate T, Conte D, Mello CC. piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell. 2012 Jul 06; 150(1):65-77. PMID: 22738726.
      View in: PubMed
    8. Lee HC, Aalto AP, Yang Q, Chang SS, Huang G, Fisher D, Cha J, Poranen MM, Bamford DH, Liu Y. The DNA/RNA-dependent RNA polymerase QDE-1 generates aberrant RNA and dsRNA for RNAi in a process requiring replication protein A and a DNA helicase. PLoS Biol. 2010 Oct 05; 8(10). PMID: 20957187.
      View in: PubMed
    9. Lee HC, Li L, Gu W, Xue Z, Crosthwaite SK, Pertsemlidis A, Lewis ZA, Freitag M, Selker EU, Mello CC, Liu Y. Diverse pathways generate microRNA-like RNAs and Dicer-independent small interfering RNAs in fungi. Mol Cell. 2010 Jun 25; 38(6):803-14. PMID: 20417140.
      View in: PubMed
    10. Lee HC, Chang SS, Choudhary S, Aalto AP, Maiti M, Bamford DH, Liu Y. qiRNA is a new type of small interfering RNA induced by DNA damage. Nature. 2009 May 14; 459(7244):274-7. PMID: 19444217.
      View in: PubMed
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