Increased expression of the MBP mRNA binding protein HnRNP A2 during oligodendrocyte differentiation

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a trans-acting factor that mediates intracellular trafficking of myelin basic protein (MBP) mRNA to the myelin compartment in oligodendrocytes, is most abundant in the nucleus, but shuttles between the nucleus and cytoplasm. In the cytoplasm, it is associated with granules that transport mRNA from the cell body to the processes of oligodendrocytes. We found that the overall level of hnRNP A2 increased in oligodendrocytes as they differentiated into MBIP-positive cells, and that this augmentation was reflected primarily in the cytoplasmic pool of hnRNP A2 present in the form of granules. The extranuclear distribution of hnRNP A2 was also observed in brain during the period of myelination in vivo. Methylation and phosphorylation have been implicated previously in the nuclear to cytoplasmic distribution of hnRNPs, so we used drugs that block methylation and phosphorylation of hnRNPs to assess their effect on hnRNP A2 distribution and mRNA trafficking. Cultures treated with adenosine dialdehyde (AdOx), an inhibitor of S-adenosyl-L-homocysteine hydrolase, or with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a drug that inhibits casein kinase 2 (CK2), maintained the preferential nuclear distribution of hnRNP A2. Treatment with either drug affected the transport of RNA trafficking granules that remained confined to the cell body. (C) 2004 Wiley-Liss, Inc.

MHC promoter polymorphism in grey wolves and domestic dogs

A functional immune system requires a tight control over major histocompatibility complex (MHC) gene transcription, as the abnormal MHC expression patterns of severe immunodeficiency and autoimmune diseases demonstrate. Although the regulation of MHC expression has been well documented in humans and mice, little is known in other species. In this study, we detail the level of polymorphism in wolf and dog MHC gene promoters. The promoter regions of the DRB, DQA and DQB locus were sequenced in 90 wolves and 90 dogs. The level of polymorphism was high in the DQB promoters, with variation found within functionally relevant regions, including binding sites for transcription factors. Clear associations between DQB promoters and exon 2 alleles were noted in wolves, indicating strong linkage disequilibrium in this region. Low levels of polymorphism were found within the DRB and DQA promoter regions. However, a variable site was identified within the T box, a TNF-alpha response element, of the DQA promoter. Furthermore, we identified a previously unrecognised 18-base-pair deletion within exon 1 of the DQB locus.