Poly(A) tail dynamics, non-adenine incorporation and alternative polyadenylation shape the host transcriptome in COVID-19 pathogenesis

TL;DR

This study explores how changes in RNA processing, including poly(A) tail dynamics and non-adenine modifications, affect the host transcriptome during COVID-19.

Contribution

The study introduces a multi-omic approach combining long-read sequencing to analyze poly(A) tail dynamics and non-A modifications in whole blood transcriptomes of COVID-19 patients.

Findings

Significant alterations in gene expression patterns were observed in COVID-19 patients compared to healthy controls.

Poly(A) tail lengths and non-adenine modifications showed notable changes in response to SARS-CoV-2 infection.

The findings highlight the interplay between viral infection, host immune response, and RNA processing in COVID-19 pathogenesis.

Abstract

The COVID-19 pandemic has had a profound global impact since its emergence in late 2019. Characterized by a wide spectrum of clinical manifestations, COVID-19 has necessitated extensive research into the host-pathogen interactions that drive disease progression. Understanding the molecular mechanisms underlying the host response to SARS-CoV-2 infection is crucial for the development of effective therapeutic interventions and preventative strategies. This study employed a multi-omic approach that combined direct RNA sequencing (DRS) and Illumina cDNA sequencing to investigate whole blood transcriptomic profiles in COVID-19 patients. By leveraging the unique capabilities of Nanopore DRS, which provides long-read sequencing data, we were able to capture not only gene expression levels but also crucial poly(A) tail length fluctuations and non-adenine residue (non-A) modifications. This comprehensive analysis allowed us to identify differentially expressed genes and explore the impact of these poly(A) modifications on function within the context of COVID-19. Findings reveal significant alterations in gene expression patterns, poly(A) tail lengths and non-A modifications in COVID-19 patients compared to healthy controls. Results provide valuable insights into the complex interplay between viral infection, host immune response, and RNA processing, contributing to a deeper understanding of COVID-19 pathogenesis.

The online version contains supplementary material available at 10.1038/s41598-025-21969-5.

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