Interferon inducible pseudouridine modification in human mRNA by quantitative nanopore profiling

Genome Biol. 2021 Dec 6;22(1):330. doi: 10.1186/s13059-021-02557-y.

Abstract

Pseudouridine (Ψ) is an abundant mRNA modification in mammalian transcriptome, but its functions have remained elusive due to the difficulty of transcriptome-wide mapping. We develop a nanopore native RNA sequencing method for quantitative Ψ prediction (NanoPsu) that utilizes native content training, machine learning modeling, and single-read linkage analysis. Biologically, we find interferon inducible Ψ modifications in interferon-stimulated gene transcripts which are consistent with a role of Ψ in enabling efficacy of mRNA vaccines.

Keywords: Interferon; Machine learning; Nanopore sequencing; Pseudouridine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteria
  • Caenorhabditis elegans
  • Drosophila
  • Gene Expression Profiling / methods
  • HEK293 Cells
  • Humans
  • Interferons*
  • Machine Learning
  • Nanopores*
  • Pseudouridine / genetics*
  • Pseudouridine / metabolism*
  • RNA
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / genetics*
  • Sequence Analysis, RNA / methods
  • Transcriptome

Substances

  • RNA, Messenger
  • Pseudouridine
  • RNA
  • Interferons