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H19 RNA binds four molecules of insulin-like growth factor II mRNA-binding protein
S Runge1, F C Nielsen, J Nielsen
1RNA Regulation Centre, Institute of Molecular Biology, University of Copenhagen, DK-1307 Copenhagen, Denmark.
Abstract:
H19 RNA is a major oncofetal 2.5-kilobase untranslated RNA of unknown function. The maternally expressed H19 gene is located 90 kilobase pairs downstream from the paternally expressed insulin-like growth factor II (IGF-II) gene on human chromosome 11 and mouse chromosome 7; and due to their reciprocal imprinting and identical spatiotemporal expression, it is assumed that the two genes are functionally coupled. Here we show that human H19 RNA contains four attachment sites for the oncofetal IGF-II mRNA-binding protein (IMP) with apparent K(d) values in the 0.4-1.3 nm range. The multiple attachment sites are clustered within a 700-nucleotide segment encoded by exons 4 and 5. This 3'-terminal segment targets H19 RNA to lamellipodia and perinuclear regions in dispersed fibroblasts where IMP is also localized. The results suggest that IMP participates in H19 RNA localization and provides a link between the IGF-II and H19 genes at post-transcriptional events during mammalian development.
Insights
The oncofetal H19 RNA binds to the IGF-II mRNA-binding protein (IMP). This interaction links the H19 and IGF-II genes, suggesting a role in post-transcriptional regulation during development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- H19 RNA is a major oncofetal untranslated RNA with an unknown function.
- The H19 gene is reciprocally imprinted and co-expressed with the paternally expressed insulin-like growth factor II (IGF-II) gene.
- Functional coupling between H19 and IGF-II genes is hypothesized due to their genomic proximity and imprinted expression patterns.
Purpose of the Study:
- To investigate the functional relationship between H19 RNA and IGF-II.
- To identify potential molecular mechanisms linking H19 and IGF-II gene expression.
- To explore the role of H19 RNA in cellular localization and its interaction with proteins.
Main Methods:
- RNA-protein binding assays to characterize H19 RNA interaction with IGF-II mRNA-binding protein (IMP).
- Identification and localization of H19 RNA and IMP within dispersed fibroblasts.
- Analysis of H19 RNA sequence for potential binding sites.
Main Results:
- Human H19 RNA exhibits multiple high-affinity binding sites for IMP.
- These binding sites are located within a specific region of H19 RNA (exons 4 and 5).
- H19 RNA is localized to lamellipodia and perinuclear regions, colocalizing with IMP.
Conclusions:
- IMP binds to H19 RNA, suggesting a direct molecular link between these two entities.
- IMP mediates the cellular localization of H19 RNA.
- The findings indicate a role for IMP in the post-transcriptional regulation and functional coupling of H19 and IGF-II genes during mammalian development.