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 adapter 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 deadenylation or decapping. We observed that RNAs undergoing decay are predominantly enriched in the stress granule transcriptome while inhibition of stress granule formation via genetic ablation of G3BP1 and G3BP2 rescues RNA length. Our findings reveal RNA decay as a key component of RNA metabolism upon cellular stress that is dependent on stress granule formation.

• Klíčová slova
• RNA decay, cell biology, cell line, genetics, genomics, human, mouse, stress response,
• MeSH
• adaptorové proteiny signální transdukční metabolismus   genetika   MeSH
• DNA-helikasy metabolismus   genetika   MeSH
• exoribonukleasy * metabolismus   genetika   MeSH
• fyziologický stres * genetika   MeSH
• lidé MeSH
• proteiny asociované s mikrotubuly MeSH
• proteiny vázající poly-ADP-ribosu * metabolismus   genetika   MeSH
• proteiny vázající RNA MeSH
• ribozomy metabolismus   MeSH
• RNA-helikasy metabolismus   genetika   MeSH
• RRM proteiny * metabolismus   genetika   MeSH
• sekvenční analýza RNA * MeSH
• stabilita RNA * genetika   MeSH
• stresová tělíska metabolismus   genetika   MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• DNA-helikasy MeSH
• exoribonukleasy * MeSH
• G3BP1 protein, human MeSH Prohlížeč
• G3BP2 protein, human MeSH Prohlížeč
• proteiny asociované s mikrotubuly MeSH
• proteiny vázající poly-ADP-ribosu * MeSH
• proteiny vázající RNA MeSH
• RNA-helikasy MeSH
• RRM proteiny * MeSH
• XRN1 protein, human MeSH Prohlížeč

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 deadenylation or decapping. We observed that RNAs undergoing decay are predominantly enriched in the stress granule transcriptome while inhibition of stress granule formation via genetic ablation of G3BP1 and G3BP2 rescues RNA length. Our findings reveal RNA decay as a key determinant of RNA metabolism upon cellular stress and dependent on stress-granule formation.

• Publikační typ
• časopisecké články MeSH
• preprinty MeSH