PREreviews of “Full-length direct RNA sequencing uncovers stress-granule dependent RNA decay upon cellular stress” | PREreview

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Full-length direct RNA sequencing uncovers stress-granule dependent RNA decay upon cellular stress

by Showkat A. Dar, Sulochan Malla, Vlastimil Martinek, Matthew J. Payea, Christopher T. Lee, Jessica Martin, Aditya J. Khandeshi, Jennifer L. Martindale, Cedric Belair, and Manolis Maragkakis

Posted: September 1, 2023
Server: bioRxiv
DOI: 10.1101/2023.08.31.555629

Abstract

Cells react to stress by triggering response pathways, leading to extensive alterations in the transcriptome to restore cellular homeostasis. The role of RNA metabolism in shaping the cellular response to stress is vital, yet the global changes in RNA stability under these conditions remain unclear. In this work, we employ direct RNA sequencing with nanopores, enhanced by 5’ end adaptor ligation, to comprehensively interrogate the human transcriptome at single-molecule and nucleotide resolution. By developing a statistical framework to identify robust RNA length variations in nanopore data, we find that cellular stress induces prevalent 5’ end RNA decay that is coupled to translation and ribosome occupancy. Unlike typical RNA decay models in normal conditions, we show that stress-induced RNA decay is dependent on XRN1 but does not depend on removal of the poly(A) tail. We observed that RNAs undergoing decay are predominantly enriched in the stress granule transcriptome. Inhibition of stress granule formation via genetic ablation of G3BP1 and G3BP2 fully rescues RNA length and suppresses stress-induced decay. Our findings reveal RNA decay as a key determinant of RNA metabolism upon cellular stress and dependent on stress-granule formation.

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PREreview by Lawngreen Parrot et al. of the HHMI Transparent and Accountable Peer Review Training Pilot

Authored by Lawngreen Parrot and 1 other author of the HHMI Transparent and Accountable Peer Review Training Pilot

The manuscript “Full-length direct RNA sequencing uncovers stress-granule dependent RNA decay upon cellular stress" by Dar and colleagues uses end-to-end RNA sequencing by Nanopore to examine the effect of oxidative stress on RNA length. They observe transcript shortening under arsenite stress …

Read the PREreview by Lawngreen Parrot et al. of the HHMI Transparent and Accountable Peer Review Training Pilot
PREreview by Hickory Butterfly et al. of the HHMI Transparent and Accountable Peer Review Training Pilot

Authored by Hickory Butterfly and 1 other author of the HHMI Transparent and Accountable Peer Review Training Pilot

In this manuscript, the authors employed an end-to-end direct RNA sequencing technique called TERA-seq to study RNA decay at the single nucleotide resolution during cellular stress. Their sequencing analyses showed that a subset of RNAs have shortened 5’ ends upon cellular stress conditions that …

Read the PREreview by Hickory Butterfly et al. of the HHMI Transparent and Accountable Peer Review Training Pilot