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

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-

SUBMITTER: Guminska N 

PROVIDER: S-EPMC11920217 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature