AN AMINO-TERMINAL TETRAPEPTIDE SPECIFIES COTRANSLATIONAL DEGRADATION OF BETA-TUBULIN BUT NOT ALPHA-TUBULIN MESSENGER-RNAS

The steady-state level of alpha- and beta-tubulin synthesis is autoreg ulated by a posttranscriptional mechanism that selectively alters alph a- and beta-tubulin mRNA levels in response to changes in the unassemb led tubulin subunit concentration. For beta-tubulin mRNAs, previous ef forts have shown that this is the result of a selective mRNA degradati on mechanism which involves cotranslational recognition of the nascent amino-terminal beta-tubulin tetrapeptide as it emerges from the ribos ome. Site-directed mutagenesis is now used to determine that the minim al sequence requirement for conferring the full range of beta-tubulin autoregulation is the amino terminal tetrapeptide MR(E/D)I. Although t ubulin-dependent changes in alpha-tubulin mRNA levels are shown to res ult from changes in cytoplasmic mRNA stability, transfection of wild-t ype and mutated alpha-tubulin genes reveals that alpha- and beta-tubul in mRNA degradation is not mediated through a common pathway. Not only does the amino-terminal alpha-tubulin tetrapeptide MREC fail to confe r regulated mRNA degradation, neither, wild-type alpha-tubulin transge nes nor an alpha-tubulin gene mutated to encode an amino-terminal MREI yields mRNAs that are autoregulated. Further, although slowing riboso me transit accelerates the autoregulated degradation of endogenous alp ha- and beta-tubulin mRNAs, degradation of alpha-tubulin transgene mRN As is not enhanced, and in one case, the mRNA is actually stabilized. We conclude that, despite similarities, alpha- and beta-tubulin mRNA d estabilization pathways utilize divergent determinants to link RNA ins tability to tubulin subunit concentrations.