Direct profiling of non-adenosines in poly(A) tails of endogenous and therapeutic mRNAs with Ninetails.

作者信息

Gumińska Natalia, Matylla-Kulińska Katarzyna, Krawczyk Paweł S, Maj Michał, Orzeł Wiktoria, Mackiewicz Zuzanna, Brouze Aleksandra, Mroczek Seweryn, Dziembowski Andrzej

机构信息

Laboratory of RNA Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.

Faculty of Biology, University of Warsaw, Warsaw, Poland.

出版信息

Nat Commun. 2025 Mar 18;16(1):2664. doi: 10.1038/s41467-025-57787-6.

Abstract

Stability and translation of mRNAs, both endogenous and therapeutic, is determined by poly(A) tail. Direct RNA sequencing enables single-molecule measurements of poly(A) lengths, avoiding amplification bias. It also holds potential for observation of non-adenosines within poly(A), known to influence mRNA fate. However, there is no computational method to detect composite tails in Direct Sequencing data. To address this gap, we introduce the Ninetails, a neural network-based tool that accurately identifies and quantifies non-adenosines in poly(A) tails. Examination of different biological contexts revealed widespread non-adenosine decorations, with frequencies influenced by the origin of poly(A) tails differing by mRNA class, cell type, and species. Notably, substrates of cytoplasmic TENT5-polymerases and mitochondrially encoded mRNAs are enriched in composite tails. For mRNA therapeutics, we show that the composition of poly(A) tails in mRNA vaccines is dynamic during its cellular lifetime and that the manufacturing protocol of synthetic mRNAs affects the purity of poly(A) tails.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b2/11920217/d66a18e0aa69/41467_2025_57787_Fig1_HTML.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索