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CD Spectroscopy to Study DNA-Protein Interactions
Published on: February 10, 2022
The discoidin domain receptor 1 gene has a functional A2RE sequence
Barbara Roig1, Sílvia Moyano, Lourdes Martorell
1Hospital Universitari Psiquiàtric Institut Pere Mata, IISPV, Universitat Rovira i Virgili, Reus, Spain. barbara.roig@urv.cat
Journal of Neurochemistry
|November 15, 2011
Summary
Discoidin domain receptor 1 (DDR1) mRNA has an A2RE-like sequence, suggesting hnRNP A2/B1 involvement in its transport. This impacts myelin gene expression and oligodendrocyte function.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Discoidin domain receptor 1 (DDR1) is found in myelin oligodendrocytes and co-localizes with myelin basic protein (MBP).
- MBP mRNA transport to oligodendrocyte processes relies on hnRNP A2/B1 binding to an A2RE sequence.
- DDR1 alternative splicing generates five isoforms (DDR1a-e).
Purpose of the Study:
- To investigate if DDR1 mRNA contains a functional A2RE sequence.
- To explore the role of hnRNP A2/B1 in DDR1 mRNA splicing and transport.
- To determine the impact of the rs2267641 polymorphism on DDR1 isoform expression.
Main Methods:
- In silico analysis to identify A2RE-like sequences in DDR1 mRNA.
- Immunofluorescence to observe DDR1 and hnRNP A2/B1 co-localization in oligodendrocytes.
- Analysis of human brain tissue and differentiated HOG16 cells with siRNA knockdown.
Main Results:
- An A2RE-like sequence was identified in human DDR1 mRNA.
- DDR1 and hnRNP A2/B1 co-localize in oligodendrocytes.
- The rs2267641 polymorphism correlates with DDR1b and DDR1c mRNA levels.
- hnRNP A2/B1 knockdown altered DDR1b and DDR1c mRNA and protein levels.
Conclusions:
- The DDR1 A2RE-like sequence is functionally involved in hnRNP A2/B1-mediated splicing and transport of DDR1c mRNA.
- This mechanism influences myelin gene expression and oligodendrocyte function.
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