POSTTRANSCRIPTIONAL EVENTS ARE RESPONSIBLE FOR LOW EXPRESSION OF MYELIN BASIC-PROTEIN IN MYELIN DEFICIENT MICE - ROLE OF NATURAL ANTISENSE RNA

Myelin deficient mice (mld) are characterized by tandem duplication of the gense coding for myelin basic protein (MBP). The upstream gene contains a large inversion of the 3' region which includes exons 3-7, and therefore it cannot give rise to mature mRNA and functional protein. MBP and MBP mRNA concentrations in mld brains constitute only ~2% of the concentrations present in normal mice. The overall transcription rate of the Mbp gene is normal. In order to explain the discrepancy between mRNA concentration and transcription rate, we studied transcription of each individual gene. The two genes were transcribed independently, although some uninterrupted transcription could not be excluded. The rate of transcription of the upstream gene was higher than that of the downstream gene. This difference was reflected in the concentration of sense and antisense RNA found in nuclei. Our results indicate that the low concentration of the mature mRNA cannot be caused by transcriptional interference. High concentration of nuclear antisense RNA strongly suggests that post-transcriptional regulation occurs in mld mice through formation of double stranded RNA.