scholarly journals Integrative Regulatory Mapping Indicates that the RNA-Binding Protein HuR Couples Pre-mRNA Processing and mRNA Stability

2011 ◽  
Vol 43 (3) ◽  
pp. 327-339 ◽  
Author(s):  
Neelanjan Mukherjee ◽  
David L. Corcoran ◽  
Jeffrey D. Nusbaum ◽  
David W. Reid ◽  
Stoyan Georgiev ◽  
...  
2007 ◽  
Vol 28 (2) ◽  
pp. 772-783 ◽  
Author(s):  
Frank Vumbaca ◽  
Kathryn N. Phoenix ◽  
Daniel Rodriguez-Pinto ◽  
David K. Han ◽  
Kevin P. Claffey

ABSTRACT Vascular endothelial growth factor (VEGF) is a key angiogenic factor expressed under restricted nutrient and oxygen conditions in most solid tumors. The expression of VEGF under hypoxic conditions requires transcription through activated hypoxia-inducible factor 1 (HIF-1), increased mRNA stability, and facilitated translation. This study identified double-stranded RNA-binding protein 76/NF90 (DRBP76/NF90), a specific isoform of the DRBP family, as a VEGF mRNA-binding protein which plays a key role in VEGF mRNA stability and protein synthesis under hypoxia. The DRBP76/NF90 protein binds to a human VEGF 3′ untranslated mRNA stability element. RNA interference targeting the DRBP76/NF90 isoform limited hypoxia-inducible VEGF mRNA and protein expression with no change in HIF-1-dependent transcriptional activity. Stable repression of DRBP76/NF90 in MDA-MB-435 breast cancer cells demonstrated reduced polysome-associated VEGF mRNA levels under hypoxic conditions and reduced mRNA stability. Transient overexpression of the DRBP76/NF90 protein increased both VEGF mRNA and protein levels synthesized under normoxic and hypoxic conditions. Cells with stable repression of the DRBP76/NF90 isoform showed reduced tumorigenic and angiogenic potential in an orthotopic breast tumor model. These data demonstrate that the DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading onto polysomes and translation under hypoxic conditions, thus promoting breast cancer growth and angiogenesis in vivo.


PLoS Genetics ◽  
2013 ◽  
Vol 9 (3) ◽  
pp. e1003367 ◽  
Author(s):  
Laetitia Davidovic ◽  
Nelly Durand ◽  
Olfa Khalfallah ◽  
Ricardo Tabet ◽  
Pascal Barbry ◽  
...  

2019 ◽  
Vol 31 ◽  
pp. 67-74 ◽  
Author(s):  
Yong-gang Hong ◽  
Guo-shu Xu ◽  
Guan-yu Yu ◽  
Ji-dian Zhou ◽  
Qi-zhi Liu ◽  
...  

2008 ◽  
Vol 22 (17) ◽  
pp. 2347-2352 ◽  
Author(s):  
J. Souopgui ◽  
B. Rust, ◽  
J. Vanhomwegen ◽  
J. Heasman ◽  
K. A. Henningfeld ◽  
...  

2009 ◽  
Vol 20 (9) ◽  
pp. 2473-2485 ◽  
Author(s):  
Ryosuke Satoh ◽  
Takahiro Morita ◽  
Hirofumi Takada ◽  
Ayako Kita ◽  
Shunji Ishiwata ◽  
...  

Myosin II is an essential component of the actomyosin contractile ring and plays a crucial role in cytokinesis by generating the forces necessary for contraction of the actomyosin ring. Cdc4 is an essential myosin II light chain in fission yeast and is required for cytokinesis. In various eukaryotes, the phosphorylation of myosin is well documented as a primary means of activating myosin II, but little is known about the regulatory mechanisms of Cdc4. Here, we isolated Nrd1, an RNA-binding protein with RNA-recognition motifs, as a multicopy suppressor of cdc4 mutants. Notably, we demonstrated that Nrd1 binds and stabilizes Cdc4 mRNA, thereby suppressing the cytokinesis defects of the cdc4 mutants. Importantly, Pmk1 mitogen-activated protein kinase (MAPK) directly phosphorylates Nrd1, thereby negatively regulating the binding activity of Nrd1 to Cdc4 mRNA. Consistently, the inactivation of Pmk1 MAPK signaling, as well as Nrd1 overexpression, stabilized the Cdc4 mRNA level, thereby suppressing the cytokinesis defects associated with the cdc4 mutants. In addition, we demonstrated the cell cycle–dependent regulation of Pmk1/Nrd1 signaling. Together, our results indicate that Nrd1 plays a role in the regulation of Cdc4 mRNA stability; moreover, our study is the first to demonstrate the posttranscriptional regulation of myosin expression by MAPK signaling.


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