Reduction of AUF1-mediated follistatin mRNA decay during glucose starvation protects cells from apoptosis

Gao, Xiangwei; Dong, Haojie; Chen, Lin; Sheng, Jinghao; Zhang, Fan; Su, Jinfeng; Xu, Zhengping

doi:10.1093/nar/gku778

Cited by 26 publications

(17 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cellular glucose levels also regulate AUF1 shuttling to the nucleus and AMPK is important for this effect (Gao et al ., 2014). Here, we found that AMPK is also important in mediating the effects of metformin on AUF1 redistribution to the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

et al. 2016

View full text Add to dashboard Cite

SummaryMetformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age‐related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA‐processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post‐transcriptional mechanism involving the RNA‐binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life‐extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR‐20a, miR‐34a, miR‐130a, miR‐106b, miR‐125, and let‐7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1‐dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence‐associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age‐related disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The canonical ARE sequence is distinguished by the presence of AUUUA pentamers, frequently in multiple and/or overlapping arrangements, within a U‐rich region that may range in size from 40 to 150 nucleotides . Besides AUF1, these sequences provide binding sites for a diverse array of factors collectively termed ‘ARE‐binding proteins.’ Depending on the specific factor recruited, protein binding may stabilize or destabilize the mRNA, or alternatively alter its translational potential …”

Section: The Auf1 Protein Familymentioning

confidence: 99%

AUF1 regulation of coding and noncoding RNA

2016

View full text Add to dashboard Cite

AUF1 is a family of four RNA-binding proteins generated by alternative pre-mRNA splicing, with canonical roles in controlling the stability and/or translation of mRNA targets based on recognition of AU-rich sequences within mRNA 3′ untranslated regions. However, recent studies identifying AUF1 target sites across the transcriptome have revealed that these canonical functions are but a subset of its roles in posttranscriptional regulation of gene expression. In this review, we describe recent developments in our understanding of the RNA-binding properties of AUF1 together with their biochemical implications and roles in directing mRNA decay and translation. This is then followed by a survey of newly discovered activities for AUF1 proteins in control of miRNA synthesis and function, including miRNA assembly into miRISC complexes, miRISC targeting to mRNA substrates, interplay with an expanding network of other cellular RNA-binding proteins, and reciprocal regulatory relationships between miRNA and AUF1 synthesis. Finally, we discuss recently reported relationships between AUF1 and long noncoding RNAs and regulatory roles on viral RNA substrates. Cumulatively, these findings have significantly expanded our appreciation of the scope and diversity of AUF1 functions in the cell, and are prompting an exciting array of new questions moving forward.

show abstract

“…FST is up-regulated during glucose deprivation and plays a protective role 13 14 . We hypothesized that FST is also a SiO 2 NP-responsive protein.…”

Section: Resultsmentioning

confidence: 99%

“…The TGF-β-like molecule-neutralizing effect of FST contributes to most of its functions 10 11 12 . Recent studies showed that FST also plays a protective role under cellular stresses including oxidative stress 13 14 15 . For example, activin induces endothelial cell oxidative stress and endothelial cell dysfunction, and these effects are mitigated by follistatin 15 .…”

mentioning

confidence: 99%

Transcriptional activation of follistatin by Nrf2 protects pulmonary epithelial cells against silica nanoparticle-induced oxidative stress

Chen

Zhao

Sun

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

Silica nanoparticles (SiO2 NPs) cause oxidative stress in respiratory system. Meanwhile, human cells launch adaptive responses to overcome SiO2 NP toxicity. However, besides a few examples, the regulation of SiO2 NP-responsive proteins and their functions in SiO2 NP response remain largely unknown. In this study, we demonstrated that SiO2 NP induced the expression of follistatin (FST), a stress responsive gene, in mouse lung tissue as well as in human lung epithelial cells (A549). The levels of Ac-H3(K9/18) and H3K4me2, two active gene markers, at FST promoter region were significantly increased during SiO2 NP treatment. The induction of FST transcription was mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2), as evidenced by the decreased FST expression in Nrf2-deficient cells and the direct binding of Nrf2 to FST promoter region. Down-regulation of FST promoted SiO2 NP-induced apoptosis both in cultured cells and in mouse lung tissue. Furthermore, knockdown of FST increased while overexpression of FST decreased the expression level of NADPH oxidase 1 (NOX1) and NOX5 as well as the production of cellular reactive oxygen species (ROS). Taken together, these findings demonstrated a protective role of FST in SiO2 NP-induced oxidative stress and shed light on the interaction between SiO2 NPs and biological systems.

show abstract

Reduction of AUF1-mediated follistatin mRNA decay during glucose starvation protects cells from apoptosis

Cited by 26 publications

References 43 publications

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

AUF1 regulation of coding and noncoding RNA

Transcriptional activation of follistatin by Nrf2 protects pulmonary epithelial cells against silica nanoparticle-induced oxidative stress

Contact Info

Product

Resources

About