Simultaneous nanopore profiling of mRNA m<sup>6</sup>A and pseudouridine reveals translation coordination.

Huang, Sihao; Wylder, Adam C; Pan, Tao · Nat Biotechnol · 2024

basic_science · Level V

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Abstract

N6-methyladenosine (m<sup>6</sup>A) and pseudouridine (Ψ) are the two most abundant modifications in mammalian messenger RNA, but the coordination of their biological functions remains poorly understood. We develop a machine learning-based nanopore direct RNA sequencing method (NanoSPA) that simultaneously analyzes m<sup>6</sup>A and Ψ in the human transcriptome. Applying NanoSPA to polysome profiling, we reveal opposing transcriptomic co-occurrence of m<sup>6</sup>A and Ψ and synergistic, hierarchical effects of m<sup>6</sup>A and Ψ on the polysome.

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