scholarly journals Neuron-Specific IMP2 Overexpression by Synapsin Promoter-Driven AAV9: A Tool to Study Its Role in Axon Regeneration

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2654
Author(s):  
Sarah Blizard ◽  
Danielle Park ◽  
Natalie O’Toole ◽  
Sheeva Norooz ◽  
Martin Dela Torre ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Axon Regeneration ◽  
Viral Vector ◽  
Binding Protein ◽  
Factor Ii ◽  
Mrna Binding Protein ◽  
Specific Mrnas ◽  
Mrna Binding

Insulin-like growth factor II mRNA-binding protein (IMP) 2 is one of the three homologues (IMP1-3) that belong to a conserved family of mRNA-binding proteins. Its alternative splice product is aberrantly expressed in human hepatocellular carcinoma, and it is therefore identified as HCC. Previous works have indicated that IMP1/ZBP1 (zipcode binding protein) is critical in axon guidance and regeneration by regulating localization and translation of specific mRNAs. However, the role of IMP2 in the nervous system is largely unknown. We used the synapsin promoter-driven adeno-associated viral (AAV) 9 constructs for transgene expression both in vitro and in vivo. These viral vectors have proven to be effective to transduce the neuron-specific overexpression of IMP2 and HCC. Applying this viral vector in the injury-conditioned dorsal root ganglion (DRG) culture demonstrates that overexpression of IMP2 significantly inhibits axons regenerating from the neurons, whereas overexpression of HCC barely interrupts the process. Quantitative analysis of binding affinities of IMPs to β-actin mRNA reveals that it is closely associated with their roles in axon regeneration. Although IMPs share significant structural homology, the distinctive functions imply their different ability to localize specific mRNAs and to regulate the axonal translation.

The roles of Insulin-like growth factor-II messenger RNA (mRNA)-binding protein-3 (IMP-3) in melanoma progression

2013 ◽  
Vol 69 (2) ◽  
pp. e20-e21
Author(s):  
Chia-Yu Chu ◽  
Yi-Shuan Sheen ◽  
Kuanyin K. Lin ◽  
Meng-Chen Hsieh ◽  
Hsien-Ching Chiu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Messenger Rna ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Melanoma Progression ◽  
Factor Ii ◽  
Mrna Binding Protein ◽  
Mrna Binding

scholarly journals An Interaction between Two RNA Binding Proteins, Nab2 and Pub1, Links mRNA Processing/Export and mRNA Stability

2007 ◽  
Vol 27 (18) ◽  
pp. 6569-6579 ◽  
Author(s):  
Luciano H. Apponi ◽  
Seth M. Kelly ◽  
Michelle T. Harreman ◽  
Alexander N. Lehner ◽  
Anita H. Corbett ◽  
...  
Keyword(s):  
Mrna Stability ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Tail Length ◽  
Functional Link ◽  
Mrna Binding Protein ◽  
Mrna Binding

ABSTRACT mRNA stability is modulated by elements in the mRNA transcript and their cognate RNA binding proteins. Poly(U) binding protein 1 (Pub1) is a cytoplasmic Saccharomyces cerevisiae mRNA binding protein that stabilizes transcripts containing AU-rich elements (AREs) or stabilizer elements (STEs). In a yeast two-hybrid screen, we identified nuclear poly(A) binding protein 2 (Nab2) as being a Pub1-interacting protein. Nab2 is an essential nucleocytoplasmic shuttling mRNA binding protein that regulates poly(A) tail length and mRNA export. The interaction between Pub1 and Nab2 was confirmed by copurification and in vitro binding assays. The interaction is mediated by the Nab2 zinc finger domain. Analysis of the functional link between these proteins reveals that Nab2, like Pub1, can modulate the stability of specific mRNA transcripts. The half-life of the RPS16B transcript, an ARE-like sequence-containing Pub1 target, is decreased in both nab2-1 and nab2-67 mutants. In contrast, GCN4, an STE-containing Pub1 target, is not affected. Similar results were obtained for other ARE- and STE-containing Pub1 target transcripts. Further analysis reveals that the ARE-like sequence is necessary for Nab2-mediated transcript stabilization. These results suggest that Nab2 functions together with Pub1 to modulate mRNA stability and strengthen a model where nuclear events are coupled to the control of mRNA turnover in the cytoplasm.

scholarly journals Dwarfism and Impaired Gut Development in Insulin-Like Growth Factor II mRNA-Binding Protein 1-Deficient Mice

2004 ◽  
Vol 24 (10) ◽  
pp. 4448-4464 ◽  
Author(s):  
Thomas V. O. Hansen ◽  
Niels A. Hammer ◽  
Jacob Nielsen ◽  
Mette Madsen ◽  
Charlotte Dalbaeck ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Rna Binding ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Ii ◽  
Extracellular Matrix Components ◽  
Mrna Binding Protein ◽  
Mrna Binding ◽  
Deficient Mice

ABSTRACT Insulin-like growth factor II mRNA-binding protein 1 (IMP1) belongs to a family of RNA-binding proteins implicated in mRNA localization, turnover, and translational control. Mouse IMP1 is expressed during early development, and an increase in expression occurs around embryonic day 12.5 (E12.5). To characterize the physiological role of IMP1, we generated IMP1-deficient mice carrying a gene trap insertion in the Imp1 gene. Imp1−/− mice were on average 40% smaller than wild-type and heterozygous sex-matched littermates. Growth retardation was apparent from E17.5 and remained permanent into adult life. Moreover, Imp1−/− mice exhibited high perinatal mortality, and only 50% were alive 3 days after birth. In contrast to most other organs, intestinal epithelial cells continue to express IMP1 postnatally, and Imp1−/− mice exhibited impaired development of the intestine, with small and misshapen villi and twisted colon crypts. Analysis of target mRNAs and global expression profiling at E12.5 indicated that Igf2 translation was downregulated, whereas the postnatal intestine showed reduced expression of transcripts encoding extracellular matrix components, such as galectin- 1, lumican, tenascin-C, procollagen transcripts, and the Hsp47 procollagen chaperone. Taken together, the results demonstrate that IMP1 is essential for normal growth and development. Moreover, IMP1 may facilitate intestinal morphogenesis via regulation of extracellular matrix formation.

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