Characterization of Rat ARPP‐21 mRNA: Sequence Analysis, Tissue Distribution, and Regulation

Abstract

ARPP-21 (cyclic AMP-regulated phosphoprotein; Mr = 21,000) is a cytosolic neuronal phosphoprotein that is highly enriched in the striatum and in other dopaminoceptive regions of the brain. The state of phosphorylation of ARPP-21 is also regulated by vasoactive intestinal peptide in intact cells. We previously reported the sequence analysis of bovine ARPP-21 cDNA and have now characterized rat ARPP-21 cDNA to study further the molecular biology of this protein. The sequence of the coding region is 82 and 85% identical at the nucleotide and amino acid levels, respectively, between the two species. There are two major classes of clones, differing only in the lengths of their 3' untranslated ends, suggesting that the different ARPP-21 mRNAs are derived from the use of alternate polyadenylation sites. Both major mRNA species, 2.6 and 0.7 kb, are present at the highest concentration in the striatum, followed by the cortex, consistent with previous immunocytochemical results. Southern blot analysis reveals a simple hybridization pattern, consistent with the presence of a single rat gene encoding ARPP-21. The steady-state levels of the ARPP-21 mRNAs are developmentally regulated but, in the neonatal and mature animal, are not altered following 6-hydroxydopamine lesions of the substantia nigra or by pharmacologic treatments that up-regulate the D1- or D2-dopamine receptors.