Organisms, including mammals, invertebrates, and plants have evolved sophisticated and conserved innate immune responses to protect themselves from pathogen attacks. In these systems, host immune responses and disease resistance are achieved by modulation of a large array of genes, but how these processes are regulated is still largely unclear. Small RNAs are non-coding regulatory RNA molecules that control gene expression by mediating mRNA degradation, translational inhibition, or chromatin modification. Our work and those of others have demonstrated a role of host endogenous small RNAs, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), in antibacterial innate immunity. We discovered that several pathogen-induced host endogenous siRNAs, including natural antisense transcripts-derived siRNAs (nat-siRNAs) and long siRNAs (lsiRNAs), facilitate host immune responses by posttranscriptionally silencing the negative regulators of plant immune systems. Epigenetic changes were also observed in bacteria-infected plants, however, the role of small RNA-guided DNA methylation and chromatin modification in plant immunity has not been explored. Using Arabidopsis as a model system and Illumina deep sequencing as a platform, we recently profiled the small RNA population after bacterium-challenge and identified diverse classes of endogenous small RNAs that are regulated by the infection of bacterial pathogens. We hypothesize that these pathogen-responsive small RNAs regulate the expression of genes involved in host immune responses by silencing regulators of host immunity transcriptionally or post-transcriptionally. We propose to investigate the regulation, biogenesis, and function of these pathogen-responsive small RNAs. Specifically, we will perform in depth characterization of several newly identified miRNAs, nat-siRNAs, lsiRNAs, and clustered hc-siRNAs that are particularly regulated by various strains of the bacterium Pseudomonas syringae. Predicted target genes of these small RNAs will be validated and subjected to functional analysis. These targets are likely to be components involved in plant immune response pathways. We will also characterize the hc-siRNAs that directed DNA methylation in response to bacterial infection. We will generate a whole-genome DNA-methylation map before and after bacterial infection, and correlate the siRNAs, DNA methylation, and pathogen-responsive gene expression. The proposed research will significantly advance our understanding of the mechanisms and functions of small RNAs involved in host innate immunity.

Public Health Relevance

Multicellular eukaryotes, including mammals, invertebrates, and plants have evolved sophisticated and conserved innate immune responses to protect themselves from pathogen attack. The proposed research will significantly advance our understanding of the mechanisms and function of small RNA-mediated gene regulation in innate immunity using the model organism Arabidopsis thaliana.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM093008-04
Application #
8499367
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Bender, Michael T
Project Start
2010-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$270,414
Indirect Cost
$88,897
Name
University of California Riverside
Department
Other Basic Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
Cai, Qiang; Qiao, Lulu; Wang, Ming et al. (2018) Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes. Science 360:1126-1129
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, 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; 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, Ming; Jin, Hailing (2017) Spray-Induced Gene Silencing: a Powerful Innovative Strategy for Crop Protection. Trends Microbiol 25:4-6
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
Wang, Ming; Weiberg, Arne; Jin, Hailing (2015) Pathogen small RNAs: a new class of effectors for pathogen attacks. Mol Plant Pathol 16:219-23
Weiberg, Arne; Bellinger, Marschal; Jin, Hailing (2015) Conversations between kingdoms: small RNAs. Curr Opin Biotechnol 32:207-215

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