, a Long Noncoding RNA Essential for Global Oxygen Sensing in Humans

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Nov 22

PMID 37992175

Authors

Zhi Chen

Chan Chen

Lei Xiao

Rongfu Tu

Miaomiao Yu

Donghai Wang

Wenqian Kang

Meng Han

Hao Huang

Hudan Liu

Bing Zhao

Guoliang Qing

Affiliations

Soon will be listed here.

Abstract

Adaptation to low levels of oxygen (hypoxia) is a universal biological feature across metazoans. However, the unique mechanisms how different species sense oxygen deprivation remain unresolved. Here, we functionally characterize a novel long noncoding RNA (lncRNA), , which we termed hypoxia-induced lncRNA for polo-like kinase 1 (PLK1) stabilization (). exhibits appreciable basal expression exclusively in a wide variety of human normal and cancer cells and is robustly induced by hypoxia-inducible factor 1α (HIF1α). binds to PLK1 and sequesters it from proteasomal degradation. Stabilized PLK1 directly phosphorylates HIF1α and enhances its stability, constituting a positive feed-forward circuit that reinforces oxygen sensing by HIF1α. depletion triggers catastrophic adaptation defect during hypoxia in both normal and cancer cells. These findings introduce a mechanism that underlies the HIF1α identity deeply interconnected with PLK1 integrity and identify the -PLK1-HIF1α pathway as a unique oxygen-sensing axis in the regulation of human physiological and pathogenic processes.

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