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 #
5R01GM061146-14
Application #
8438417
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
2000-05-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
14
Fiscal Year
2013
Total Cost
$244,168
Indirect Cost
$71,625
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
Li, Chenlong; Gu, Lianfeng; Gao, Lei et al. (2016) Concerted genomic targeting of H3K27 demethylase REF6 and chromatin-remodeling ATPase BRM in Arabidopsis. Nat Genet 48:687-93
Cui, Jie; You, Chenjiang; Chen, Xuemei (2016) The evolution of microRNAs in plants. Curr Opin Plant Biol 35:61-67
Li, Shaofang; Liu, Lin; Li, Shengben et al. (2016) SUVH1, a Su(var)3-9 family member, promotes the expression of genes targeted by DNA methylation. Nucleic Acids Res 44:608-20
Liu, Lin; Chen, Xuemei (2016) RNA Quality Control as a Key to Suppressing RNA Silencing of Endogenous Genes in Plants. Mol Plant 9:826-36
Huang, Zhigang; Shi, Ting; Zheng, Binglian et al. (2016) APETALA2 antagonizes the transcriptional activity of AGAMOUS in regulating floral stem cells in Arabidopsis thaliana. New Phytol :
Li, Chenlong; Chen, Chen; Gao, Lei et al. (2015) The Arabidopsis SWI2/SNF2 chromatin Remodeler BRAHMA regulates polycomb function during vegetative development and directly activates the flowering repressor gene SVP. PLoS Genet 11:e1004944
Wang, Xiaoyan; Zhang, Shuxin; Dou, Yongchao et al. (2015) Synergistic and independent actions of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs in Arabidopsis. PLoS Genet 11:e1005091
Zhao, Qiong; Gao, Caiji; Lee, PoShing et al. (2015) Fast-suppressor screening for new components in protein trafficking, organelle biogenesis and silencing pathway in Arabidopsis thaliana using DEX-inducible FREE1-RNAi plants. J Genet Genomics 42:319-30
Sanei, Maryam; Chen, Xuemei (2015) Mechanisms of microRNA turnover. Curr Opin Plant Biol 27:199-206
Tu, Bin; Liu, Li; Xu, Chi et al. (2015) Distinct and cooperative activities of HESO1 and URT1 nucleotidyl transferases in microRNA turnover in Arabidopsis. PLoS Genet 11:e1005119

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