A fundamental question in developmental biology is how pluripotent stem cells are maintained and how they differentiate into various lineages in multicellular organisms. Flower development in the model plant Arabidopsis thaliana offers a great system to address key questions in stem cell biology. One of our long-term goals is to uncover the mechanisms that govern the maintenance and termination of floral stem cells. We and others have uncovered an as yet incomplete network of three transcription factors superimposed by a microRNA (miRNA)-based posttranscriptional mechanism that governs the maintenance of floral stem cells. In the proposed research, we will expand this network by identifying core components at the heart of floral stem cell regulation. We will 1) identify target genes of the two key transcription factors, 2) incorporate the newly identified floral stem cell regulators, ARF2, ARF3 and ARF4, and the small RNA that regulates the three transcription factor genes into the existing framework of floral stem cell regulation, and 3) probe the role of the Polycomb group proteins in floral stem cell termination. miRNAs are sequence-specific regulatory molecules that impact numerous biological processes including development. The trans-acting siRNAs (ta-siRNAs) are a class of plant-specific, miRNA-like small RNAs with important developmental roles. Another long-term research goal is to dissect the general mechanisms underlying the biogenesis and mode of action of small RNAs and to study how the biogenesis or activities of specific miRNAs or ta-siRNAs are modulated in development. Whereas the major framework of miRNA biogenesis is established, how miRNAs inhibit target gene expression is highly controversial at present. The field is at its very early stages of understanding how the activities of specific small RNAs are regulated in developmental contexts. A key to dissecting the mode of action of miRNAs and understanding how small RNA activity is regulated in development is to identify proteins that mediate or modulate the activities of small RNAs. We have identified two such proteins, AGO10 and AMP1 in small RNA-mediated target gene regulation. The proposed research is aimed at uncovering the molecular functions of these two proteins. The proposed work will undoubtedly provide novel insights into stem cell regulation and miRNA function. Understanding how stem cells are maintained and terminated in plants will help derive basic principles that govern stem cell biology and contribute to the ultimate use of stem cells in regenerative medicine. Due to the highly conserved mechanisms underlying miRNA biogenesis and function between plants and animals, an advance in the mechanistic understanding of miRNA function from our work will directly impact our abilities to harness the power of small RNAs to fight pathogens and human diseases.

Public Health Relevance

Understanding how stem cells are maintained and how they differentiate is key to harnessing the power of stem cells for regenerative medicine in the future. This research will reveal major players in the transcriptional and post-transcriptional networks that govern the temporal regulation of stem cells. This research will also advance our understanding of the mode of action of miRNAs, regulatory molecules that impact all aspects of biology and whose mis-regulation is associated with human diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM061146-11A1S1
Application #
8078793
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
2010-09-01
Project End
2011-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
11
Fiscal Year
2010
Total Cost
$114,169
Indirect Cost
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
Chen, Jiayi; Liu, Li; You, Chenjiang et al. (2018) Structural and biochemical insights into small RNA 3' end trimming by Arabidopsis SDN1. Nat Commun 9:3585
Ma, Xuan; Liu, Chunyan; Gu, Lianfeng et al. (2018) TarHunter, a tool for predicting conserved microRNA targets and target mimics in plants. Bioinformatics 34:1574-1576
Huang, Zhigang; Shi, Ting; Zheng, Binglian et al. (2017) APETALA2 antagonizes the transcriptional activity of AGAMOUS in regulating floral stem cells in Arabidopsis thaliana. New Phytol 215:1197-1209
Yu, Yu; Ji, Lijuan; Le, Brandon H et al. (2017) ARGONAUTE10 promotes the degradation of miR165/6 through the SDN1 and SDN2 exonucleases in Arabidopsis. PLoS Biol 15:e2001272
Li, Dongming; Palanca, Ana Marie S; Won, So Youn et al. (2017) The MBD7 complex promotes expression of methylated transgenes without significantly altering their methylation status. Elife 6:
Jia, Tianran; Zhang, Bailong; You, Chenjiang et al. (2017) The Arabidopsis MOS4-Associated Complex Promotes MicroRNA Biogenesis and Precursor Messenger RNA Splicing. Plant Cell 29:2626-2643
Cui, Jie; You, Chenjiang; Chen, Xuemei (2017) The evolution of microRNAs in plants. Curr Opin Plant Biol 35:61-67
Yu, Yu; Jia, Tianran; Chen, Xuemei (2017) The 'how' and 'where' of plant microRNAs. New Phytol 216:1002-1017
Su, Zhenxia; Zhao, Lihua; Zhao, Yuanyuan et al. (2017) The THO Complex Non-Cell-Autonomously Represses Female Germline Specification through the TAS3-ARF3 Module. Curr Biol 27:1597-1609.e2
Kim, Yun Ju; Wang, Ruozhong; Gao, Lei et al. (2016) POWERDRESS and HDA9 interact and promote histone H3 deacetylation at specific genomic sites in Arabidopsis. Proc Natl Acad Sci U S A 113:14858-14863

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