{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/understanding-ythdf2-mediated-mrna","title":"Understanding YTHDF2-mediated mRNA Degradation By m6A-BERT-Deg","arxiv_id":"2401.08004","date":"2024-01-15","proceeding":null,"authors":["Ting-He Zhang","Sumin Jo","Michelle Zhang","Kai Wang","Shou-Jiang Gao","Yufei Huang"],"abstract":"N6-methyladenosine (m6A) is the most abundant mRNA modification within mammalian cells, holding pivotal significance in the regulation of mRNA stability, translation, and splicing. Furthermore, it plays a critical role in the regulation of RNA degradation by primarily recruiting the YTHDF2 reader protein. However, the selective regulation of mRNA decay of the m6A-methylated mRNA through YTHDF2 binding is poorly understood. To improve our understanding, we developed m6A-BERT-Deg, a BERT model adapted for predicting YTHDF2-mediated degradation of m6A-methylated mRNAs. We meticulously assembled a high-quality training dataset by integrating multiple data sources for the HeLa cell line. To overcome the limitation of small training samples, we employed a pre-training-fine-tuning strategy by first performing a self-supervised pre-training of the model on 427,760 unlabeled m6A site sequences. The test results demonstrated the importance of this pre-training strategy in enabling m6A-BERT-Deg to outperform other benchmark models. We further conducted a comprehensive model interpretation and revealed a surprising finding that the presence of co-factors in proximity to m6A sites may disrupt YTHDF2-mediated mRNA degradation, subsequently enhancing mRNA stability. We also extended our analyses to the HEK293 cell line, shedding light on the context-dependent YTHDF2-mediated mRNA degradation.","url_abs":"https://arxiv.org/abs/2401.08004v1","url_pdf":"https://arxiv.org/pdf/2401.08004v1.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"understanding-ythdf2-mediated-mrna","repo_url":"https://github.com/tinghezhang/m6abert","is_official":1,"mentioned_in_paper":1,"mentioned_in_github":0,"framework":"pytorch","reach":null}],"tasks":[],"methods":[{"method_slug":"adam","method_name":"Adam"},{"method_slug":"attention","method_name":"Attention"},{"method_slug":"attention-dropout","method_name":"Attention Dropout"},{"method_slug":"bert","method_name":"BERT"},{"method_slug":"dense-connections","method_name":"Dense Connections"},{"method_slug":"dropout","method_name":"Dropout"},{"method_slug":"layer-normalization","method_name":"Layer Normalization"},{"method_slug":"linear-layer","method_name":"Linear Layer"},{"method_slug":"linear-warmup-with-linear-decay","method_name":"Linear Warmup With Linear Decay"},{"method_slug":"multi-head-attention","method_name":"Multi-Head Attention"},{"method_slug":"residual-connection","method_name":"Residual Connection"},{"method_slug":"softmax","method_name":"Softmax"},{"method_slug":"weight-decay","method_name":"Weight Decay"},{"method_slug":"wordpiece","method_name":"WordPiece"}],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"atlas_url":null,"mcp":null,"developers":"https://syntology.ai/developers"},"arxiv_metadata":null,"syntology_extracted_results":null}