ArticleMolecular and cellular biology2013
HuR maintains a replicative life span by repressing the ARF tumor suppressor.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Expression of targets of the RNA-binding protein AUF-1 in human airway epithelium indicates its role in cellular senescence and inflammation.Frontiers in immunology · 2023Article
- p19Biomolecules · 2020Article
- RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration.Frontiers in cell and developmental biology · 2020Article
- Loss of RNA-binding protein HuR facilitates cellular senescence through posttranscriptional regulation of TIN2 mRNA.Nucleic acids research · 2018Article
- Nucleolin phosphorylation regulates PARN deadenylase activity during cellular stress response.RNA biology · 2018Article
- Identification of tumorigenesis-related mRNAs associated with RNA-binding protein HuR in thyroid cancer cells.Oncotarget · 2016Article
- Elimination of p19JCI insight · 2016Article
- Forget transcription: translation is where the action is.Molecular and cellular biology · 2013Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p19(ARF) plays an essential role in the senescence of mouse cells, and its expression is lost by methylation or deletion of the ARF locus; otherwise, p53 is inactivated to bypass senescence. ARF expression is tightly regulated, but little is known about its posttranscriptional regulation. Here, we show that an RNA-binding protein, HuR (human antigen R), represses ARF mRNA translation, thereby maintaining the replicative life span of mouse embryonic fibroblasts (MEFs). Loss of HuR results in premature senescence, with concomitant increases in p19(ARF) but not p16(Ink4a) levels, and this senescence is not observed in ARF-null MEFs that retain an intact Ink4a locus. HuR depletion does not alter ARF transcription or stability but enhances ribosome association with ARF mRNA. Under these conditions, ARF mRNA accumulates in nucleoli, where it associates with nucleolin. Furthermore, adipose-specific deletion of the HuR gene results in increased p19(ARF) expression in aged animals, which is accompanied by decreased insulin sensitivity. Together, our findings demonstrate that p19(ARF) is also regulated at the translational level, and this translational regulation restrains the cellular life span and tissue functions in vivo.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.