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.
Sensitized piRNA reporter identifies multiple RNA processing factors involved in piRNA-mediated gene silencing.
Sensitized piRNA reporter identifies multiple RNA processing factors involved in piRNA-mediated gene silencing. Genetics. 2023 08 09; 224(4).
PMID: 37210214
Sensitized piRNA reporter identifies multiple RNA processing factors involved in piRNA-mediated gene silencing.
Sensitized piRNA reporter identifies multiple RNA processing factors involved in piRNA-mediated gene silencing. bioRxiv. 2023 Jan 22.
PMID: 36712000
GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance.
GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance. Nat Commun. 2022 09 09; 13(1):5306.
PMID: 36085149
CLASH Analyst: A Web Server to Identify In Vivo RNA-RNA Interactions from CLASH Data.
CLASH Analyst: A Web Server to Identify In Vivo RNA-RNA Interactions from CLASH Data. Noncoding RNA. 2022 Jan 12; 8(1).
PMID: 35076587
Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation.
Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation. Nat Commun. 2021 05 13; 12(1):2788.
PMID: 33986289
The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle.
The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle. Genetics. 2020 06; 215(2):421-434.
PMID: 32245789
piRTarBase: a database of piRNA targeting sites and their roles in gene regulation.
piRTarBase: a database of piRNA targeting sites and their roles in gene regulation. Nucleic Acids Res. 2019 01 08; 47(D1):D181-D187.
PMID: 30357353
pirScan: a webserver to predict piRNA targeting sites and to avoid transgene silencing in C. elegans.
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
The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes.
The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes. Science. 2018 02 02; 359(6375):587-592.
PMID: 29420292
The RNase PARN-1 Trims piRNA 3' Ends to Promote Transcriptome Surveillance in C. elegans.
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