Long-read Sequencing Can Identify RNA Isoforms and NMD Modulators

Evangelos Karousis is a Senior Researcher at the University of Bern, Switzerland and presented at the Nanopore Community Meeting 2021 on “Nanopore sequencing reveals endogenous NMD-targeted isoforms in human cells.” They began by describing what nonsense-mediated mRNA decay (NMD) can do how how they can be dangerous. Endogenous mRNAs can be targeted by NMD. In this project, they learned about NMD modulation. They isolated total RNA from single and double RNA depletions. Using a new bioinformatics pipeline, they identified endogenous NMD-sensitive mRNAs. Long-read sequencing also identified previously unannotated exons. Long-reads, Karousis noted, facilitate the identification of novel RNA isoforms. The group also compared mRNA sensitive RNAs and their features. Karousis spoke about not knowing the native function of NMD. It seems, Karousis explained, that long-read sequencing can reveal RNA isoforms targeted by NMD. It is interesting that NMD-sensitive mRNAs “derive mostly from the introduction of alternative exons.” It also seems that NMD is involved in clearing aberrant transcripts.

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What is nonsense mediated mRNA degradation (NMD), and how can we learn about it using long-read sequencing? Photo by mali maeder on Pexels.com