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Native RNA nanopore sequencing reveals antibiotic-induced loss of rRNA modifications in the A- and P-sites

Authors: Anna Delgado-Tejedor; Rebeca Medina; Oguzhan Begik; Luca Cozzuto; Judith López; Sandra Blanco; Julia Ponomarenko; +1 Authors

Native RNA nanopore sequencing reveals antibiotic-induced loss of rRNA modifications in the A- and P-sites

Abstract

The biological relevance and dynamics of mRNA modifications have been extensively studied; however, whether rRNA modifications are dynamically regulated, and under which conditions, remains unclear. Here, we systematically characterize bacterial rRNA modifications upon exposure to diverse antibiotics using native RNA nanopore sequencing. To identify significant rRNA modification changes, we develop NanoConsensus, a novel pipeline that is robust across RNA modification types, stoichiometries and coverage, with very low false positive rates, outperforming all individual algorithms tested. We then apply NanoConsensus to characterize the rRNA modification landscape upon antibiotic exposure, finding that rRNA modification profiles are altered in the vicinity of A and P-sites of the ribosome, in an antibiotic-specific manner, possibly contributing to antibiotic resistance. Our work demonstrates that rRNA modification profiles can be rapidly altered in response to environmental exposures, and provides a robust workflow to study rRNA modification dynamics in any species, in a scalable and reproducible manner.

Keywords

Sequence Analysis, RNA, Science, Q, Microbiology, Article, Computational biology and bioinformatics, Anti-Bacterial Agents, Nanopore Sequencing, RNA, Bacterial, Antibiotics, RNA, Ribosomal, Escherichia coli, RNA Processing, Post-Transcriptional, Ribosomes, Algorithms

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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