The nonsense-mediated decay RNA-surveillance pathway facilitates the hypoxia response by C. elegans
- 1Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology Cambridge, MA 02139, USA.
Abstract
Hypoxia (decreased O₂) induces physiological, metabolic, and behavioral changes. The major hypoxia response pathway is conserved from nematodes to mammals and is driven by activation of the HIF (hypoxia inducible factor) family of transcription factors. Despite a fundamental role of the HIF pathway in regulating cellular homeostasis in response to hypoxic stress, interactions between the HIF pathway and cellular quality control pathways are largely unknown. Using an unbiased genetic screen, we found that in C. elegans nonsense-mediated decay (NMD), an evolutionarily conserved mechanism of RNA surveillance, acts in parallel to HIF-1 to selectively enhance specific aspects of the response to HIF-1 activation, possibly through coregulation of a distinct subset of HIF-1-up-regulated genes. Our findings reveal a functional integration between oxygen sensing and RNA surveillance and establish NMD as a key regulator of specific aspects of the HIF-1-driven transcriptional program and physiological response.
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BibTeX
@article{diehl2026nonsensemediated,
title = {{The nonsense-mediated decay RNA-surveillance pathway facilitates the hypoxia response by C. elegans}},
author = {Calista Diehl and H. Robert Horvitz},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aej4259},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aej4259},
note = {CC BY},
}
RIS
TY - JOUR
TI - The nonsense-mediated decay RNA-surveillance pathway facilitates the hypoxia response by C. elegans
AU - Calista Diehl
AU - H. Robert Horvitz
PY - 2026
DA - 2026/10/28
JO - Science Advances
DO - 10.1126/sciadv.aej4259
UR - https://www.science.org/doi/abs/10.1126/sciadv.aej4259
AB - Hypoxia (decreased O₂) induces physiological, metabolic, and behavioral changes. The major hypoxia response pathway is conserved from nematodes to mammals and is driven by activation of the HIF (hypoxia inducible factor) family of transcription factors. Despite a fundamental role of the HIF pathway in regulating cellular homeostasis in response to hypoxic stress, interactions between the HIF pathway and cellular quality control pathways are largely unknown. Using an unbiased genetic screen, we found that in C. elegans nonsense-mediated decay (NMD), an evolutionarily conserved mechanism of RNA surveillance, acts in parallel to HIF-1 to selectively enhance specific aspects of the response to HIF-1 activation, possibly through coregulation of a distinct subset of HIF-1-up-regulated genes. Our findings reveal a functional integration between oxygen sensing and RNA surveillance and establish NMD as a key regulator of specific aspects of the HIF-1-driven transcriptional program and physiological response.
SN - 2375-2548
ER -