TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISMS REGULATING NEUROFILAMENT AND TUBULIN GENE-EXPRESSION DURING NORMAL DEVELOPMENT OF THE RAT-BRAIN

The transcription of the beta(II)-, beta(IV)- and alpha 1-tubulin genes as well as that of the three neurofilament genes, NF-L, NF-M and NF-H, was examined during the course of postnatal brain development. Changes in the transcriptional activity of these genes were studied using run-off transcription assays with nuclei isolated from the rat cerebral cortex at postnatal days P2, P5, P10 and adult stages. Northern blotting of total RNA isolated from the cerebral cortex was used to compare changes in steady-state mRNA levels with transcriptional changes that occurred in the cerebral cortex during the postnatal interval. Nuclear run-off assays showed that beta(II)- and alpha 1-tubulin gene transcription rates were maximal from P2-P5 and declined at later times. Changes in the steady-state mRNA levels for these two genes followed the same general pattern as transcription, but in the case of beta(II)-tubulin mRNA, were more dramatic. beta(IV)-tubulin gene transcription dropped between P2 and P5 and then increased progressively to the adult stage, coordinate with an increase in beta(IV)-tubulin steady-state mRNA levels. NF-L and NF-H genes showed similar patterns of transcriptional change during the postnatal interval, with maximal rates of transcription at P5 followed by a decline at later times. The steady-state levels of NF-L and NF-H mRNAs changed in a manner opposite to that of transcription and increased progressively during the postnatal interval. This suggests that mRNA stabilization is the main factor regulating the steady-state levels of NF-L and NF-H mRNAs in postnatal brain. For the NF-M gene, the developmental transcription pattern was also dissociated from steady-state mRNA level changes, but differed from the transcription patterns of the NF-L and NF-H genes. This suggests the importance of post-transcriptional mechanisms in regulating NF-M mRNA levels in brain and also indicates that some differences exist in the regulatory mechanisms which control NF-M compared to NF-L and NF-H mRNA levels.