XenmiR: A resource of Xenopus microRNA expression patterns

Lead Research Organisation: University of East Anglia
Department Name: Biological Sciences

Abstract

MicroRNAs (miRNA) are short, non-coding RNAs around 22 nucleotides long. They block gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. They are involved in controlling various mechanisms during development by regulating gene expression at the post transcriptional level. Some are highly conserved amongst diverse organisms and many of them have highly specific spatio-temporal expression patterns during development. The aim of this project as part of an Industrial Partnership Agreement (IPA) with Exiqon is to determine the expression patterns of miRNAs expressed during Xenopus development using LNA oligonucleotides. These modified oligonucleotides were developed by Exiqon and bind with high affinity and high specificity to specific targets. The results will be made freely available to the scientific community. Similar studies have been done in zebrafish and chicken to the great benefit of those communities and in a broader sense to the developmental biology community as a whole. This is because it can be difficult to identify miRNAs from particular tissues. Researchers can use the expression data resources to target miRNAs to carry out functional experiments specific to their model system. Adding the complete expression patterns for Xenopus will complement the studies done in zebrafish and chick and will provide an invaluable resource for the Xenopus community. Adding Xenopus to the list of species where expression patterns are known will allow for careful analysis of similarities and differences in expression patterns and thus provide valuable comparative data. This will in turn lead to insight into the possible species specific functions of miRNAs. In addition, functional experiments such as gain of function and loss of function experiments, which are relatively easy in Xenopus, can be carried out on specific miRNAs identified from the expression database.

Technical Summary

In Xenopus 184 miRNAs have been identified and confirmed and are registered in miRBase (http://microrna.sanger.ac.uk/). Our industrial collaborator Exiqon will produce miRCURYTM LNA oligonucleotides to these miRNAs, which we will then use to carry out in situ hybridisations on wholemount embryos and sections to determine the specific expression patterns of those miRNAs at different stages of Xenopus tropicalis and laevis development, including early development and metamorphosis. The results will be collected and made available to the scientific community in a database, which we will set up and run called XenmiR. The results will also be available via the established and widely used Xenbase and QuickImage databases.

Publications

10 25 50
 
Description MicroRNAs (miRNA) are short, non-coding RNAs around 22 nucleotides long. They are involved in controlling various
mechanisms during development by regulating or controlling gene expression. They block gene expression either by translational repression or by causing the degradation of the messenger RNAs they bind to. They are highly conserved amongst diverse organisms and many of them are expressed in specific cell types.

The aim of this project is to determine the expression patterns of miRNAs expressed during Xenopus development.

Similar studies have been done in zebrafish and chicken to the great benefit of those communities and in a broader sense to the developmental biology community as a whole.

Adding the complete expression patterns for Xenopus will provide an invaluable resource for the Xenopus community. Adding Xenopus to the list of species where expression patterns are known will allow for careful analysis of similarities and differences in expression patterns. This will in turn lead to insight into the possible functions of miRNAs.
Exploitation Route The expression patterns we have characterised for 175 miRNAs are freely available to the scientific community through Xenbase (http://www.xenbase.org/entry/) and Xenmark (http://genomics.nimr.mrc.ac.uk/apps/XenMARK/). Researchers studying specific miRNAs will be able to look at their expression pattern in Xenopus embryos to give them insight into where and when the miRNA is expressed in the developing embryo
Sectors Education,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description 1. Our findings are freely available on the web and are being used by other researchers to look at the expression patterns of specific miRNAs 2. We identified a number of miRNAs that seem to be expressed in and embryonic tissue called the Neural Crest. This formed the basis of a PhD studentship application. A BBSRC funded DTP student has subsequently been recruited and has started on this project 3. our findings have been published. Ahmed et al 2015. PLoS One
Sector Education,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural

 
Description BBSRC DTP studentship
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2013 
End 10/2017
 
Description BBSRC DTP studentship
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2017 
End 09/2021
 
Title XenmiR 
Description A collection of expression patterns of 175 Xenopus miRNAs at different stages of embryonic development 
Type Of Material Database/Collection of data 
Year Produced 2013 
Provided To Others? Yes  
Impact None yet 
URL http://www.xenbase.org/geneExpression/static/miRNA/body/mirTable.jsp
 
Description XenmiR 
Organisation Medical Research Council (MRC)
Department MRC National Institute for Medical Research (NIMR)
Country United Kingdom 
Sector Academic/University 
PI Contribution We provided the miRNA expression pictures
Collaborator Contribution Dr Gilchrist added our images to the XenMARK database. This enables the images to be part of this database which is used by the Xenopus and General Scientific Communities
Impact This collaboration is multidisciplinary as Dr Gilchrist provides the computational support we do not have. Ahmed et al. 2015. PLoS One
Start Year 2011
 
Description miRNAs in xenopus development 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution sharing data and doing miRNA in situs
Collaborator Contribution They have specific miRNAs that they are interested in based on small RNA sequencing. They would like to confirm their results using our XenmiR database and further in situs
Impact Ahmed et al. 2015. Plos One
Start Year 2014
 
Description the function of miR-219 and miR196a in Neural Crest development 
Organisation Curie Institute Paris (Institut Curie)
Country France 
Sector Academic/University 
PI Contribution My PhD student went over to Paris to do the experiments as they are experts in this field. The results have been analysed and used for further research. We are continuing to meet and talk and a manuscript may be prepared in the coming year
Collaborator Contribution They have helped with the generation of the material that went for sequencing. they have provided additional knowledge and advice
Impact I spoke further with the PI in France and along with a colleague in London the three of us initiated an EU FP7 grant application for an ITN. An application was made in Jan 2018. This was unsuccessful. A resubmission was made in Jan 2019
Start Year 2016
 
Description Xenopus microRNA expression patterns 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact We have now uploaded approx 750 images to the Xenmark web pages. This means that researchers around the world have access to the miRNA expression patterns we have found in an easily searchable database. We have uploaded ~750 images to Xenmark (http://genomics.nimr.mrc.ac.uk/apps/XenMARK/) showing Xenopus miRNA expression patterns. These can now be used by the scientific community. We have paid for storage of these images on a UEA server for the next five years
The storage has been continued for another 5 years

no actual impacts realised to date
Year(s) Of Engagement Activity 2013,2014,2015,2016,2017,2018,2019