Kinnaird J H, Burns P A, Fincham J R
Department of Genetics, University of Edinburgh, Scotland.
J Mol Biol. 1991 Oct 5;221(3):733-6. doi: 10.1016/0022-2836(91)80167-s.
As the result of two mutually compensating frameshift mutations, three successive codons with third-position A were generated in the Neurospora crassa am (NADP-specific glutamate dehydrogenase: GDH) gene. These codons do not occur at all elsewhere in the gene and only infrequently in other highly expressed Neurospora genes. The double-frameshift strain produces only 25 to 35% of the normal level of GDH, whether measured as enzyme activity or as immunoprecipitable protein, but its level of GDH mRNA is normal. Although the modified enzyme is somewhat more heat-sensitive than the wild-type in vitro, its stability in vivo was found to be indistinguishable from that of the wild-type. It is concluded that the introduction of consecutive rare codons reduces the efficiency of translation of the mRNA. The possible mechanisms of such an effect are discussed.
