Uncovering the isoform-resolution kinetic landscape of nonsense-mediated mRNA decay with EZbakR DOI Creative Commons
Justin W. Mabin, Isaac W. Vock, Martin Machyna

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Cellular RNA levels are a product of synthesis and degradation kinetics, which can differ among transcripts the same gene. An important cause isoform-specific decay is nonsense-mediated mRNA (NMD) pathway, degrades with premature termination codons (PTCs) other features. Understanding NMD functions requires strategies to quantify isoform kinetics; however, current approaches remain limited. Methods like nucleotide-recoding RNA-seq (NR-seq) enable insights into but existing bioinformatic tools do not provide robust, rate constant estimates. We extend EZbakR-suite by implementing strategy infer isoform-level kinetics from short-read NR-seq data. This approach uncovers unexpected variability in efficiency conserved PTC-containing exons rapid subset mRNAs lacking PTCs. Our findings highlight effects competition between pathways, mechanistic established correlates, identify transcript features promoting efficient decay.

Language: Английский

Uncovering the isoform-resolution kinetic landscape of nonsense-mediated mRNA decay with EZbakR DOI Creative Commons
Justin W. Mabin, Isaac W. Vock, Martin Machyna

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Cellular RNA levels are a product of synthesis and degradation kinetics, which can differ among transcripts the same gene. An important cause isoform-specific decay is nonsense-mediated mRNA (NMD) pathway, degrades with premature termination codons (PTCs) other features. Understanding NMD functions requires strategies to quantify isoform kinetics; however, current approaches remain limited. Methods like nucleotide-recoding RNA-seq (NR-seq) enable insights into but existing bioinformatic tools do not provide robust, rate constant estimates. We extend EZbakR-suite by implementing strategy infer isoform-level kinetics from short-read NR-seq data. This approach uncovers unexpected variability in efficiency conserved PTC-containing exons rapid subset mRNAs lacking PTCs. Our findings highlight effects competition between pathways, mechanistic established correlates, identify transcript features promoting efficient decay.

Language: Английский

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