Loss of RNA-binding protein HuR facilitates cellular senescence through posttranscriptional regulation of TIN2 mRNA

Ji Hoon Lee, Misun Jung, Juyeong Hong, Mi Kyung Kim, In Kwon Chung

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cellular senescence can be induced by high levels of reactive oxygen species (ROS) produced by mitochondria. However, the mechanism by which elevated mitochondrial ROS levels are produced during replicative senescence is not yet fully understood. Here, we report that loss of the RNA-binding protein, human antigen R (HuR), during replicative senescence leads to an increase in ROS levels through enhanced mitochondrial localization of the telomeric protein TIN2. HuR binds to the 3 untranslated region of TIN2 mRNA. This association decreases TIN2 protein levels by both destabilizing TIN2 mRNA and reducing its translation. Conversely, depletion of HuR levels enhances TIN2 expression, leading to increased mitochondrial targeting of TIN2. Mitochondrial localization of TIN2 increases ROS levels, which contributes to induction and maintenance of cellular senescence. Our findings provide compelling evidence for a novel role of HuR in controlling the process of cellular senescence by regulating TIN2-mediated mitochondrial ROS production, and for a useful therapeutic route for modulating intracellular ROS levels in treating both aging-related complications and cancer.

Original languageEnglish
Pages (from-to)4271-4285
Number of pages15
JournalNucleic acids research
Volume46
Issue number8
DOIs
Publication statusPublished - 2018 Jan 1

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RNA-Binding Proteins
Cell Aging
Reactive Oxygen Species
Antigens
Messenger RNA
3' Untranslated Regions
Mitochondria
Proteins
Maintenance
Neoplasms

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Lee, Ji Hoon ; Jung, Misun ; Hong, Juyeong ; Kim, Mi Kyung ; Chung, In Kwon. / Loss of RNA-binding protein HuR facilitates cellular senescence through posttranscriptional regulation of TIN2 mRNA. In: Nucleic acids research. 2018 ; Vol. 46, No. 8. pp. 4271-4285.
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Loss of RNA-binding protein HuR facilitates cellular senescence through posttranscriptional regulation of TIN2 mRNA. / Lee, Ji Hoon; Jung, Misun; Hong, Juyeong; Kim, Mi Kyung; Chung, In Kwon.

In: Nucleic acids research, Vol. 46, No. 8, 01.01.2018, p. 4271-4285.

Research output: Contribution to journalArticle

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