Association of Purα with RNAs Homologous to 7 SL Determines Its Binding Ability to the Myelin Basic Protein Promoter DNA Sequence

Abstract Cell type and developmental stage expression of the myelin basic protein (MBP) gene in mouse brain is regulated at the transcriptional level. Earlier studies from our laboratory have led to the identification of a DNA binding protein from mouse brain, named Purα, which interacts with the MB1 regulatory motif of the MBP and stimulates its transcription in glial cells. In this report, we demonstrate that a cellular RNA, with significant homology to 7 SL RNA is associated with Purα. Results from band shift competition studies indicate that Purα-associated RNA (PU-RNA), inhibits the interaction of immunopurified Purα with the MB1 DNA sequence. Results from Northern blot studies indicated that PU-RNA is expressed during various stages of brain development. Of interest, this RNA was found in association with Purα that was produced in the mouse brain at the early stage of brain development. Results from Northwestern analysis using a PU-RNA probe identified the regions within Purα that are important for Purα/PU-RNA association. Production of Purα at the early stage of brain development and its association with PU-RNA at this stage, when Purα exhibits poor binding ability to the MB1 DNA sequence, suggests that PU-RNA may function as a co-factor that negatively regulates Purα interaction with the MBP promoter sequence.