Award details

The role of RNA structures in plant response to temperature

Reference	BB/L025000/1
Principal Investigator / Supervisor	Dr Yiliang Ding
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	Cell and Develop Biology
Funding type	Research
Value (£)	1,124,160
Status	Completed
Type	Fellowships
Start date	07/08/2014
End date	06/08/2019
Duration	60 months

Abstract

Previous studies on RNA structure have mainly relied on in vitro synthesized RNAs or in silico predictions, neither of which reflect the natural situation in vivo. I have established the first platform to measure RNA structures in vivo at both the genome-wide scale and for targeted low abundance mRNAs. This platform allows us to study global RNA structural changes, as well as targeted individual mRNAs, under a variety of conditions, including cold and heat stress. This proposed study aims to elucidate the role of RNA structure in the post-transcriptional regulation of gene expression in response to different temperatures. Firstly, in vivo RNA structural mapping will be undertaken in Arabidopsis thaliana under different temperature regimes. By global comparison between different temperatures, I will identify potential plant specific RNA thermometers (RNA regions within the 5'UTR that show structural shifts in response to temperature). Moreover, together with previous studies on polyribosome association during heat stress, I will determine how the global RNA structural changes correlate with translational efficiency. Additionally, I will explore the role of RNA structure during RNA maturation under different temperature regimes. This genome-wide analysis will provide many RNA candidates for further study. Individual plant specific RNA thermometers will be identified and characterized. I will mutate essential nucleotides required for sensing temperature and assess their corresponding biological function via transgenic assays. Tertiary contacts and conformational dynamics of the RNA thermometers will be assayed using Single-Molecule FRET. Lastly, I will develop a user-friendly web server to analyze, predict and visualize in vivo RNA structures under different temperatures in Arabidopsis. In summary, this proposed research will reveal the function of RNA structure in the post-transcriptional regulation of gene expression in response to differences in temperature.

Summary

Global warming has the potential to widely suppress agricultural yields. One of the effects of global warming is an increased occurrence of temperature extremes and these are particularly destructive of our crop plants. According to the global annual agriculture report, agricultural yields will drop by up to 20% by the year 2050 due to global climate change. Previous studies have also shown grain yield declines by 10% for each 1 degree increase. Thus, in order to avoid severe food crises caused by global warming, it is important to adapt our crop plants to withstand extreme temperature changes. My proposed research is to understand how plants respond to temperature extremes and how to regulate this response to make plants more adaptable to climate change. Most previous scientific studies have focused on gene regulation at the DNA level, however, regulation at this level is neither particularly rapid, nor does it correlate well with protein levels, which are the key output for gene regulation. My proposed research is to explore how the regulation of gene expression occurs at the RNA level, which can be rapid and more directly correlated with protein levels. RNA, in contrast to DNA, is very flexible and more responsive to different cellular conditions, in particular varying temperature. For instance, RNA forms more base pairing structures under cold conditions, while maintaining single strandedness at higher temperatures. These changes in RNA structure will have differing effects on a range of processes that control protein levels, such as ribosome binding, RNA processing and RNA stability. By taking advantage of this flexibility in RNA structure, plants can adapt to different temperature conditions quickly and reversibly via changes in protein level. My proposed research is to explore RNA structures at specific temperatures to realize modalities of gene regulation controlled by shifts in RNA structure. My previous work has developed a novel and powerful platform to measure in vivo RNA structures with high resolution over more than 10,000 genes. My proposed research is to compare the differences in global RNA structure under different temperature conditions. This will allow me to identify RNAs with different temperature-controlled structures that may directly regulate gene expression, putative RNA thermometers. My proposed research will open up a novel methodology for the study of gene regulation in plants. This methodology can also be applied to other abiotic stresses such as drought stress, mechanic stress, water stress, etc., as well as biotic stresses. A user-friendly web-based server of a corresponding bioinformatics toolkit will be established in my proposed research for analyzing, predicting and visualizing individual RNA structures of interest.

Impact Summary

This proposed research will elucidate the role of RNA structure in the post-transcriptional regulation of gene expression in response to different temperatures. I will take advantage of my novel and powerful platform established during my postdoctoral research to study global in vivo RNA structural changes, as well as targeted individual mRNAs, under a variety of conditions, including cold and heat stress. The knowledge obtained from this proposed research will provide a new gene regulatory mechanism in response to temperature, which will impact the development of novel strategic approaches to improve plant adaptation to climate change. Furthermore, this work will reveal the utility of the platform I have developed for the analysis of dynamic changes to RNA structure. This will likely have broad implications for many fields of research including the medical sciences. One result from this work is potential intellectual property. Any potential IP generated from this proposed research will be assessed for patent protection. .The novel and transformative nature of the technology I have developed may well incur interest from the private sector. RNA structure is likely important in many different processes of eukaryotic cells, including human diseases. While I have no intention of establishing a private venture at this stage in my career, I believe that the platforms I have developed have potential for commercial enterprise. Another result from this proposed research is a web-based server with detailed in vivo RNA structural information for thousands of mRNAs. This will raise a broad range of interests in the academic community and will impact the development of new collaborations as well as new research directions. The proposed research opens up an entirely new field of study in plant sciences which provides both new methodologies and new scientific viewpoints. This new field may in the long term be applied to the study of other abiotic stresses such as drought stress, mechanical stress, water stress and biotic stresses. Therefore, this proposed research could benefit a broad range of plant disciplines with potential impacts on agricultural improvements. I will engage in outreach activities such as participating in the Teacher-Scientist Network (TSN) and give public lectures on the role of RNA structures in response to stress. JIC has an excellent communications department that supports such public engagement activities.

Committee	Research Committee B (Plants, microbes, food & sustainability)
Research Topics	Plant Science, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	Fellowship - David Phillips Fellowship (DF) [1995-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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