Analysis of chimeric reads characterises the diverse targetome of AGO2-mediated regulation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F23%3A00133649" target="_blank" >RIV/00216224:14740/23:00133649 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41598-023-49757-z" target="_blank" >https://www.nature.com/articles/s41598-023-49757-z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-023-49757-z" target="_blank" >10.1038/s41598-023-49757-z</a>

Result language

angličtina

Original language name

Analysis of chimeric reads characterises the diverse targetome of AGO2-mediated regulation

Original language description

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/.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

9

Pages from-to

1-9

UT code for WoS article

001136279200030

EID of the result in the Scopus database

2-s2.0-85180195179