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The interplay of HuR and miR-3134 in regulation of AU rich transcriptome

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Title The interplay of HuR and miR-3134 in regulation of AU rich transcriptome
 
Creator Sharma, Shivani
Verma, Suneer
Vasudevan, Madavan
Samanta, Subhasis
Thakur, Jitendra K.
Kulshreshtha, Ritu
 
Subject MicroRNA
miR-3134
AU rich elements
HuR
Breast cancer
 
Description Accepted date: 20 Jun 2013
MicroRNAs and AU Rich element (ARE)-mediated degradation of transcripts are thought to be two independent means of gene regulation at the post-transcriptional level. However, since their site of action is the same (3'UTR of mRNA), there exists a high probability that specific miRNAs may bind to AREs and, thus, interact with ARE-binding proteins (ARE-BPs) to regulate transcript levels. In this study, we have characterized AREs as potential targets of hsa-miR-3134. An analysis of the global gene expression profile of breast cancer cell line MCF7 overexpressing miR-3134 revealed the presence of at least one AUUUA element in the 3'-UTRs of 63% of miR-3134 regulated protein coding genes. Quantitative RT-PCR or 3'UTR luciferase assays show that miR-3134 mediates an up to 4-8-fold increase in the levels of ARE bearing transcripts-SOX9, VEGFA, and EGFR, while mutated miR-3134 shows a decreased effect. The miR-3134-mediated increase in transcript levels was unaffected by treatment with transcription inhibitor (actinomycin D), indicating that miR-3134 enhances transcript stability. To investigate a possible interplay between miR-3134 and a prototype ARE-BP, HuR, we compared their overexpression transcriptome profiles. Interestingly, up to 80% of miR-3134-regulated genes were also regulated by HuR. Overexpression studies of HuR alone or in combination with miR-3134 shows that wt miR-3134 but not a mutated miR-3134 promotes stabilization of HuR-regulated transcripts SOX9, VEGFA, and EGFR as confirmed by qRT-PCR or RNA-immunoprecipitation experiments. Overall, this report suggests that collaboration between ARE-binding microRNAs and ARE-binding proteins could be a general mechanism of 3'-UTR mediated regulation of gene expression in human cells.
RK acknowledges support from the Department of Biotechnology,
GOI for a RGYI grant. We acknowledge Prof Alok Bhattacharya,
School of Life Sciences, Jawaharlal Nehru University for extend-
ing the lab facilities funded and supported by the Department of
Biotechnology for experimental work. SS1 thanks the Department
of Biotechnology for a Junior Research Fellowship. SS2 acknowledges fellowship from the DBT-RA program. JKT acknowledges
funding from NIPGR core grant. We acknowledge Dr Stefan
Oehler for carefully editing this manuscript.
 
Date 2015-11-18T08:40:38Z
2015-11-18T08:40:38Z
2013
 
Type Article
 
Identifier RNA Biol., 10(8): 1283-1290
2161-5063
http://172.16.0.77:8080/jspui/handle/123456789/367
http://www.tandfonline.com/doi/full/10.4161/rna.25482
10.4161/rna.25482
 
Language en_US
 
Publisher Taylor & Francis Group