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 #
5R01GM061146-13
Application #
8241084
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
2000-05-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
13
Fiscal Year
2012
Total Cost
$257,674
Indirect Cost
$76,970
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
Liu, Xigang; Gao, Lei; Dinh, Thanh Theresa et al. (2014) DNA topoisomerase I affects polycomb group protein-mediated epigenetic regulation and plant development by altering nucleosome distribution in Arabidopsis. Plant Cell 26:2803-17
Kim, Yun Ju; Maizel, Alexis; Chen, Xuemei (2014) Traffic into silence: endomembranes and post-transcriptional RNA silencing. EMBO J 33:968-80
Liu, Xigang; Dinh, Thanh Theresa; Li, Dongming et al. (2014) AUXIN RESPONSE FACTOR 3 integrates the functions of AGAMOUS and APETALA2 in floral meristem determinacy. Plant J 80:629-41
Li, Shengben; Liu, Lin; Zhuang, Xiaohong et al. (2013) MicroRNAs inhibit the translation of target mRNAs on the endoplasmic reticulum in Arabidopsis. Cell 153:562-74
Rogers, Kestrel; Chen, Xuemei (2013) Biogenesis, turnover, and mode of action of plant microRNAs. Plant Cell 25:2383-99
Yumul, Rae Eden; Kim, Yun Ju; Liu, Xigang et al. (2013) POWERDRESS and diversified expression of the MIR172 gene family bolster the floral stem cell network. PLoS Genet 9:e1003218
Zhao, Yuanyuan; Yu, Yu; Zhai, Jixian et al. (2012) The Arabidopsis nucleotidyl transferase HESO1 uridylates unmethylated small RNAs to trigger their degradation. Curr Biol 22:689-94
Dinh, Thanh Theresa; Girke, Thomas; Liu, Xigang et al. (2012) The floral homeotic protein APETALA2 recognizes and acts through an AT-rich sequence element. Development 139:1978-86
Zheng, Binglian; Chen, Xuemei; McCormick, Sheila (2011) The anaphase-promoting complex is a dual integrator that regulates both MicroRNA-mediated transcriptional regulation of cyclin B1 and degradation of Cyclin B1 during Arabidopsis male gametophyte development. Plant Cell 23:1033-46
Liu, Xigang; Kim, Yun Ju; Müller, Ralf et al. (2011) AGAMOUS terminates floral stem cell maintenance in Arabidopsis by directly repressing WUSCHEL through recruitment of Polycomb Group proteins. Plant Cell 23:3654-70

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