Abstract
RNA secondary str uct ures play essential roles in the formation of the tertiary str uct ure and function of a transcript. Recent genome-wide studies highlight significant potential for RNA str uct ures in the mammalian genome. Ho w e v er, a major challenge is assigning functional roles to these str uct ured RNAs. In this study, we conduct a guilt-b y -association analy sis of clusters of computationally predicted conserved RNA str uct ure (CRSs) in human untranslated regions (UTRs) to associate them with gene functions. We filtered a broad pool of ∼50 0 0 0 0 human CRSs for UTR o v erlap, resulting in 4734 and 24 754 CRSs from the 5 ' and 3 ' UTR of protein-coding genes, respectively. We separately clustered these CR Ss f or both sets using RNAscClust, obtaining 793 and 2403 clusters, each containing an a v erage of fiv e CR Ss per cluster. We identified o v errepresented binding sites for 60 and 43 RNA-binding proteins co-localizing with the clustered CRSs. Furthermore, 104 and 441 clusters from the 5 _ and 3 _ UTRs, respectiv ely, sho w ed enrichment for various Gene Ontologies, including biological processes such as 'signal transduction', 'nerv ous sy stem de v elopment', molecular functions lik e 'transferase activity' and the cellular components such as 'synapse' among others. Our study shows that significant functional insights can be gained by clustering RNA str uct ures based on their str uct ural characteristics.
Originalsprog | Engelsk |
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Artikelnummer | lqae089 |
Tidsskrift | NAR Genomics and Bioinformatics |
Vol/bind | 6 |
Udgave nummer | 3 |
Antal sider | 16 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:We thank Christian Anthon for helping to configure and run-ning the RNAscClust pipeline on the computing cluster us-ing slurm queuing system at the Center for non-coding RNA in Technology and Health Author contributions : V.P.G. pre-processed the data and implemented the CRS clustering using RNAscClust. M.M. and A.J. worked on the proper implementation of the pipeline. A.M.W. and V.P.G. developed the selection criteria for the rep-resentative CRSs. V.P.G. carried post-processing of the clus-ters, performed all the analysis and drafted the manuscript. J.G. made the study design. R.B., S.E.S. and J.G. supervised the study. All authors edited and reviewed the manuscript. Innovation Fund Denmark [4108-00008B and 4096-00001B to J.G.]; Danish Research Council [9041-00317B to J.G.].
Publisher Copyright:
© The Author(s) 2024.