RhoB mRNA is stabilized by HuR after UV light

Westmark, Cara J.; Bartleson, Virginia B.; Malter, James S.

doi:10.1038/sj.onc.1208224

Cited by 43 publications

(43 citation statements)

References 62 publications

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“…Furthermore, HuR dissociation from premRNA in response to DOXO may reflect its partial relocalization from nucleus to cytoplasm in response to DNA damage (Fig. 5i) 43,48,49 . Altogether, we propose the following model (Fig.…”

Section: Discussionmentioning

confidence: 99%

A recently evolved class of alternative 3′-terminal exons involved in cell cycle regulation by topoisomerase inhibitors

et al. 2014

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Alternative 3 0 -terminal exons, which use intronic polyadenylation sites, are generally less conserved and expressed at lower levels than the last exon of genes. Here we discover a class of human genes, in which the last exon appeared recently during evolution, and the major gene product uses an alternative 3 0 -terminal exon corresponding to the ancestral last exon of the gene. This novel class of alternative 3 0 -terminal exons are downregulated on a large scale by doxorubicin, a cytostatic drug targeting topoisomerase II, and play a role in cell cycle regulation, including centromere-kinetochore assembly. The RNA-binding protein HuR/ ELAVL1 is a major regulator of this specific set of alternative 3 0 -terminal exons. HuR binding to the alternative 3 0 -terminal exon in the pre-messenger RNA promotes its splicing, and is reduced by topoisomerase inhibitors. These findings provide new insights into the evolution, function and molecular regulation of alternative 3 0 -terminal exons.

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Section: Discussionmentioning

confidence: 99%

A recently evolved class of alternative 3′-terminal exons involved in cell cycle regulation by topoisomerase inhibitors

et al. 2014

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“…However, the half life of this mRNA increases from 1 to 3 h after UV exposure (161). This change in mRNA stability is associated with specific binding of HuR to its 3¢UTR coupled with nucleocytoplasmic shuttling of HuR, increasing mRNA stability and directing the transcript for translation (161). Therefore, RhoB expression is post-transcriptionally regulated in response to UV light, independent of p53.…”

Section: Uv Light Increases the Stability Of Specific Transcriptsmentioning

confidence: 99%

“…The 3¢UTR of this mRNA contains several AREs and other U-rich sequences, so the mRNA is short lived (161). However, the half life of this mRNA increases from 1 to 3 h after UV exposure (161). This change in mRNA stability is associated with specific binding of HuR to its 3¢UTR coupled with nucleocytoplasmic shuttling of HuR, increasing mRNA stability and directing the transcript for translation (161).…”

Section: Uv Light Increases the Stability Of Specific Transcriptsmentioning

confidence: 99%

“…UV-induced transcription of the RHoB MRNA is dependent on CCAATbinding factor and activating transcription factor 2 (47). The 3¢UTR of this mRNA contains several AREs and other U-rich sequences, so the mRNA is short lived (161). However, the half life of this mRNA increases from 1 to 3 h after UV exposure (161).…”

Section: Uv Light Increases the Stability Of Specific Transcriptsmentioning

confidence: 99%

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Post-Transcriptional Regulation of DNA Damage-Responsive Gene Expression

McKay

2014

Antioxidants & Redox Signaling

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Significance: Production of proteins requires the synthesis, maturation, and export of mRNAs before their translation in the cytoplasm. Endogenous and exogenous sources of DNA damage pose a challenge to the coordinated regulation of gene expression, because the integrity of the DNA template can be compromised by DNA lesions. Cells recognize and respond to this DNA damage through a variety of DNA damage responses (DDRs). Failure to deal with DNA damage appropriately can lead to genomic instability and cancer. Recent Advances: The p53 tumor suppressor plays a dominant role in DDR-dependent changes in gene expression, but this transcription factor is not solely responsible for all changes. Recent evidence indicates that RNA metabolism is integral to DDRs as well. In particular, post-transcriptional processes are emerging as important contributors to these complex responses. Critical Issues: Transcriptional, post-transcriptional, and translational regulation of gene expression is subject to changes in response to DNA damage. How these processes are intertwined in the unfolding of DDR is not fully understood. Future Directions: Many complex regulatory responses combine to determine cell fate after DNA damage. Understanding how transcriptional, post-transcriptional, and translational processes interdigitate to create a web of regulatory interactions will be one of the key challenges to fully understand DDRs. Antioxid. Redox Signal. 20, 640-654.

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“…165 On the other hand, ARE-BPs, like HuR, can stabilize ARE-containing mRNAs by blocking the recruitment of deadenylases or the exosome. 166 Interestingly, some of the seed signals recognized by miRNA overlap with AREs in the 3'UTR. Although the exact contribution of miRNAs, miRISC, AREs and ARE-BPs to mRNA decay has not been elucidated yet, recent studies have described a functional overlap between AREs-and microRNAs-mediated mRNA turnover pathways (Fig.…”

Section: Abbreviationsmentioning

confidence: 99%