Eukaryotic organisms, including animals and plants, have evolved sophisticated immune systems to protect themselves against pathogens. Small RNAs (sRNAs) are short, non-coding regulatory RNAs that induce RNA interference (RNAi) by binding to Argonaute (AGO) proteins and directing silencing of genes with complementary sequences. Our work and those of others have demonstrated that sRNAs, derived from either hosts or pathogens, function through AGO proteins and play an important role in host-pathogen interactions. However, the underlying regulatory mechanisms remain elusive. Our long-term goal is to understand the dynamic regulation of sRNAs and RNAi in host innate immunity. AGO proteins are key players of sRNA- mediated gene silencing, and we hypothesize that they are modified and regulated by their associated proteins to modulate sRNA-mediated gene silencing. Here, we seek to understand the modification and regulation of AGOs in RNAi pathway, and in host antibacterial and antifungal immune responses, by using model plant-pathogen interaction systems - Arabidopsis thaliana and its bacterial pathogen Pseudomonas syringae and aggressive fungal pathogen Botrytis cinerea. During the last funding period, we have identified diverse classes of host sRNAs regulating host immunity, and have demonstrated that Arabidopsis AGO2 (AtAGO2) is highly induced by bacterial infection and positively regulates host immunity. We have also shown that B. cinerea delivers its sRNAs into host cells and hijacks host AtAGO1 to suppress host immunity genes for successful infection. To obtain a mechanistic understanding of how AtAGO1 and AtAGO2 are regulated, we have identified their associated proteins via proteomics analysis. This renewal will study the modification and regulation of AtAGO1 and AtAGO2 by their associated proteins in RNAi pathways and host innate immunity. The output of this study will significantly advance our understanding of dynamic control of RNAi in host immune responses against pathogens, which will have great impact on both agricultural and human health.
The specific aims are: 1. Elucidate the role of protein arginine methyltransferases in modification and regulation of AtAGO function in host immunity. 2. Investigate the function of DDX3-like RNA helicases in modulating AtAGO function in host immunity. 3. Study the role of protein phosphatases in modulating AtAGO and host immunity.

Public Health Relevance

Multicellular eukaryotes, such as mammals, invertebrates, and plants, have evolved sophisticated, conserved innate immune systems to protect themselves from pathogen attacks. While supported by NIH funding, we have discovered that host and pathogen small RNAs and Argonaute proteins, the key RNA silencing pathway components, have important roles in host immune responses and host-pathogen interactions. However, the underlying regulatory mechanisms are poorly understood. The proposed research will significantly advance our understanding of the dynamic regulatory control of Argonaute proteins in RNA silencing pathways and host innate immunity using the model organism Arabidopsis thaliana and its bacterial and fungal pathogens. The output of this project will help develop novel, environmentally friendly disease control strategies and benefit both agricultural and human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM093008-06
Application #
9030945
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Bender, Michael T
Project Start
2010-07-01
Project End
2020-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
6
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California Riverside
Department
Other Basic Sciences
Type
Earth Sciences/Resources
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
Wang, Ming; Jin, Hailing (2017) Spray-Induced Gene Silencing: a Powerful Innovative Strategy for Crop Protection. Trends Microbiol 25:4-6
Wang, Ming; Thomas, Nicholas; Jin, Hailing (2017) Cross-kingdom RNA trafficking and environmental RNAi for powerful innovative pre- and post-harvest plant protection. Curr Opin Plant Biol 38:133-141
Wang, Huan; Seo, Jang-Kyun; Gao, Shang et al. (2017) Silencing of AtRAP, a target gene of a bacteria-induced small RNA, triggers antibacterial defense responses through activation of LSU2 and down-regulation of GLK1. New Phytol 215:1144-1155
Wang, Ming; Weiberg, Arne; Dellota Jr, Exequiel et al. (2017) Botrytis small RNA Bc-siR37 suppresses plant defense genes by cross-kingdom RNAi. RNA Biol 14:421-428
Wang, Ming; Weiberg, Arne; Lin, Feng-Mao et al. (2016) Bidirectional cross-kingdom RNAi and fungal uptake of external RNAs confer plant protection. Nat Plants 2:16151
Niu, Dongdong; Lii, Yifan E; Chellappan, Padmanabhan et al. (2016) miRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection. Nat Commun 7:11324
Niu, Dongdong; Xia, Jing; Jiang, Chunhao et al. (2016) Bacillus cereus AR156 primes induced systemic resistance by suppressing miR825/825* and activating defense-related genes in Arabidopsis. J Integr Plant Biol 58:426-39
Weiberg, Arne; Bellinger, Marschal; Jin, Hailing (2015) Conversations between kingdoms: small RNAs. Curr Opin Biotechnol 32:207-15
Weiberg, Arne; Jin, Hailing (2015) Small RNAs--the secret agents in the plant-pathogen interactions. Curr Opin Plant Biol 26:87-94
Zhang, Xiaoming; Niu, DongDong; Carbonell, Alberto et al. (2014) ARGONAUTE PIWI domain and microRNA duplex structure regulate small RNA sorting in Arabidopsis. Nat Commun 5:5468

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