Analysis of chimeric reads characterises the diverse targetome of AGO2-mediated regulation.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 Dec 2023
21 Dec 2023
Historique:
received:
16
09
2023
accepted:
12
12
2023
medline:
22
12
2023
pubmed:
22
12
2023
entrez:
21
12
2023
Statut:
epublish
Résumé
Argonaute proteins are instrumental in regulating RNA stability and translation. AGO2, the major mammalian Argonaute protein, is known to primarily associate with microRNAs, a family of small RNA 'guide' sequences, and identifies its targets primarily via a 'seed' mediated partial complementarity process. Despite numerous studies, a definitive experimental dataset of AGO2 'guide'-'target' interactions remains elusive. Our study employs two experimental methods-AGO2 CLASH and AGO2 eCLIP, to generate thousands of AGO2 target sites verified by chimeric reads. These chimeric reads contain both the AGO2 loaded small RNA 'guide' and the target sequence, providing a robust resource for modeling AGO2 binding preferences. Our novel analysis pipeline reveals thousands of AGO2 target sites driven by microRNAs and a significant number of AGO2 'guides' derived from fragments of other small RNAs such as tRNAs, YRNAs, snoRNAs, rRNAs, and more. We utilize convolutional neural networks to train machine learning models that accurately predict the binding potential for each 'guide' class and experimentally validate several interactions. In conclusion, our comprehensive analysis of the AGO2 targetome broadens our understanding of its 'guide' repertoire and potential function in development and disease. Moreover, we offer practical bioinformatic tools for future experiments and the prediction of AGO2 targets. All data and code from this study are freely available at https://github.com/ML-Bioinfo-CEITEC/HybriDetector/ .
Identifiants
pubmed: 38129478
doi: 10.1038/s41598-023-49757-z
pii: 10.1038/s41598-023-49757-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22895Subventions
Organisme : Grantová Agentura České Republiky,Czechia
ID : 19-10976Y
Organisme : Central European Institute of Technology
ID : LQ1601
Organisme : Grantová Agentura České Republiky
ID : 20-19617S
Organisme : OP-JAK
ID : CZ.02.01.01/00/22_008/0004575
Organisme : HORIZON EUROPE Framework Programme
ID : HORIZON-WIDERA-2022 BioGeMT 101086768
Informations de copyright
© 2023. The Author(s).
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