Computational genomics of long noncoding RNA domains across metazoans

Project Information

RNADOMAIN

Grant agreement ID: 884178

DOI

10.3030/884178

Project terminated on 28 February 2023

EC signature date 2 March 2020

Start date 1 July 2021

End date 30 June 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 196 590,72

EU contribution

€ 196 590,72

Coordinated by

UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Ireland

Periodic Reporting for period 1 - RNADOMAIN (Computational genomics of long noncoding RNA domains across metazoans)

Reporting period: 2021-07-01 to 2023-06-30

Summary of the context and overall objectives of the project

The Human Genome Project revealed a surprising discovery - the existence of many RNAs that do not encode proteins but still play important roles in cells. Understanding how these long non-coding RNAs (lncRNAs) function has been a major challenge in biology, with implications for various diseases. Recent research has shown that some repetitive regions in the genome can act as functional domains within lncRNAs, possibly explaining how these RNAs evolve and interact with other molecules. This project aimed to develop new bioinformatics methods, aided by machine learning, to gain deeper insights into lncRNA biology, identify their importance, and disseminate the information using web-accessible databases.

This project is important because it has the potential to unlock the mysteries of lncRNAs and their roles in cellular functions and disease, which could have critical implications for complex diseases such as cancer, neurodegenerative diseases, and cardiovascular diseases. By using artificial intelligence and interdisciplinary approaches, this project aimed to advance knowledge in this field and potentially lead to the development of new therapeutic strategies.

In conclusion, this project made significant progress in the field of RNA biology by mapping functional domains across the human genome through the development of a novel software tool called RIDL-pipe that finds novel domains in the genome. This has paved the way for further exploration of the functional implications of these novel domains and the dissemination of findings to the scientific community. By linking these domains to specific functional observables, valuable information has been gained to begin describing the regulatory mechanisms and pathways in which these domains are involved, providing a deeper understanding of their functional significance. Finally, the establishment of a web server has allowed for the dissemination of domain maps through an interactive web resource, providing a valuable tool for researchers interested in lncRNA research. The web server is expected to be a valuable resource for the scientific community and contribute to the advancement of our understanding of the lncRNA sequence-function code and its functional implications.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The Action aimed to lay the foundations for understanding the long non-coding RNA (lncRNA) sequence-function code by generating a high-quality, functional map of Repeat Insertion Domains of LncRNAs (RIDLs) across metazoan genomes. This Objective was divided into three Aims, which were successfully achieved during the grant period:
1. Comprehensively map RIDLs across model metazoan genomes: The project utilized state-of-the-art computational algorithms and experimental techniques to systematically identify and annotate RIDLs across the human genome. The results yielded a comprehensive map of RIDLs, providing valuable insights into their distribution, conservation, and potential functional roles.
2. Generate a functional map of functional RIDLs, with a focus on localization and disease: Building upon the RIDL map, the project further characterized the functional attributes of RIDLs, with a specific emphasis on their subcellular localization and association with diseases. Through extensive experimentation and bioinformatics analysis, the project identified functional RIDLs that play critical roles in cellular localization processes.
3. Create an open resource for dissemination and exploiting of the results: As a key deliverable of the project, an open-access database and web-based resource were established to disseminate the project's results to the wider scientific community. This resource includes the comprehensive RIDL maps, functional annotations, and associated data, providing a valuable tool for researchers to further explore the functional roles and mechanisms of lncRNA-mediated regulation.

Exploitable Results:
The results generated from the Action hold significant exploitable potential in advancing the field of lncRNA research and beyond, being useful to many researchers around the world of RNA biology. Some of the key exploitable results include:
• Comprehensive RIDL maps: The comprehensive RIDL maps generated by the project can serve as a valuable resource for researchers in the field of RNA biology, providing a foundation for further investigations into the functional roles of lncRNAs and their interactions with other molecules.
• Functional annotations: The functional annotations of RIDLs, including their subcellular localization, can be exploited to develop new hypotheses and testable predictions regarding the roles of lncRNAs in cellular processes and disease mechanisms. This knowledge can potentially lead to the development of new therapeutic strategies targeting lncRNAs for various diseases.
• Open-access database and web-based resource: The open-access database and web-based resource https://elementaldb.crg.eu/ established by the project can be further developed and expanded to include additional data and functionalities, creating a platform for collaboration, data sharing, and further research in the field of lncRNAs. This resource can also be utilized by the scientific community for data mining, analysis, and integration with other datasets to facilitate new discoveries.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Scientifically, this Action addressed a major unsolved question in the field of RNA biology: deciphering the sequence-function code of lncRNAs. By generating the first map of lncRNA elements, we paved the way to solve this critical and outstanding question in the field. On a practical angle, we created a resource that dramatically accelerates the research for RNA biology across the world.

The importance of the research lies in its potential to unravel the mysteries of lncRNAs and their role in cellular functions and disease, which could have significant implications for our understanding of complex diseases such as cancer, neurodegenerative diseases, and cardiovascular diseases. By leveraging artificial intelligence and interdisciplinary approaches, the project aimed to contribute to the advancement of knowledge in this field and potentially lead to the development of novel therapeutic strategies.

Graphical abstract for project RNADOMAIN