期刊
JOURNAL OF NEUROSCIENCE
卷 42, 期 49, 页码 9129-9141出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1630-22.2022
关键词
mRNA; nociceptor; pain; plasticity; RNA-binding; translation
资金
- National Institutes of Health-National Institute of Neurological Disorders and Stroke [R01NS100788, R01NS114018]
- National Institutes of Health-National Center for Advancing Translational Sciences [1UG3TR003149]
In this study, the researchers found that HuR protein plays an important role in translation and local control of mRNA stability. It also reveals a new biological function for a broadly conserved post-transcriptional regulatory factor.
HuR is an RNA-binding protein implicated in RNA processing, stability, and translation. Previously, we examined protein synthesis in dorsal root ganglion (DRG) neurons treated with inflammatory mediators using ribosome profiling. We found that the HuR consensus binding element was enriched in transcripts with elevated translation. HuR is expressed in the soma of nociceptors and their axons. Pharmacologic inhibition of HuR with the small molecule CMLD-2 reduced the activity of mouse and human sensory neurons. Peripheral administration of CMLD-2 in the paw or genetic elimination of HuR from sensory neurons diminished behavioral responses associated with NGF-and IL-6-induced allodynia in male and female mice. Genetic disruption of HuR altered the proximity of mRNA decay factors near a key neurotrophic factor (TrkA). Collectively, the data suggest that HuR is required for local control of mRNA stability and reveals a new biological function for a broadly conserved post-transcriptional regulatory factor.
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