title: The discoidin domain receptor 1 gene has a functional A2RE sequence.
abstract: Discoidin domain receptor 1 (DDR1) is expressed in myelin oligodendrocytes and co-localizes with myelin basic protein (MBP). Alternative splicing of DDR1 generates five isoforms designated DDR1a-e. The MBP mRNA contains an hnRNP A2 response element (A2RE) sequence that is recognized by heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, which is responsible for transport of the MBP mRNA to oligodendrocyte processes. We hypothesized that DDR1 could have a functional A2RE sequence. By in silico analysis, we identified an A2RE-like sequence in the human DDR1 mRNA. We observed nuclear and dendrite cytoplasmic immunofluorescence, indicating that DDR1 and hnRNP A2/B1 co-localize in human oligodendrocytes and in differentiated HOG16 cells. The A2RE-like sequence of DDR1 contains the single nucleotide polymorphism rs2267641, and we found that in the human brain, the minor allele is associated with lower and higher levels DDR1b and DDR1c mRNA expression, respectively. Moreover, a positive correlation between DDR1c and the myelin genes myelin-associated glycoprotein and oligodendrocyte lineage transcription factor 2 was found. Differentiated HOG16 cells transfected with an hnRNP A2/B1 siRNA simultaneously show a decrease and an increase in the DDR1c and DDR1b mRNA expression levels, respectively, which was accompanied by a decrease in DDR1 protein levels at the cytoplasmic edges. These results suggest that the DDR1 A2RE sequence is functionally involved in the hnRNP A2/B1-mediated splicing and transport of the DDR1c mRNA.
authors.affiliation: Hospital Universitari Psiquiàtric Institut Pere Mata, IISPV, Universitat Rovira i Virgili, Reus, Spain. barbara.roig@urv.cat
authors.forename: Barbara
authors.initials: B
authors.lastname: Roig
authors.forename: Sílvia
authors.initials: S
authors.lastname: Moyano
authors.forename: Lourdes
authors.initials: L
authors.lastname: Martorell
authors.forename: Javier
authors.initials: J
authors.lastname: Costas
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D000070818:Discoidin Domain Receptors; D005786:Gene Expression Regulation / Q000235:genetics; D005838:Genotype; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics*; D006801:Humans; D001523:Mental Disorders / Q000473:pathology; D018613:Microscopy, Confocal; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009778:Occipital Lobe / Q000378:metabolism* / Q000473:pathology; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034443:RNA Transport / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D014162:Transfection / Q000379:methods
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000070818:Discoidin Domain Receptors; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases; D011975:Receptors, Mitogen; C405708:OLIG2 protein, human; C439768:hnRNP A2