Propionyl-CoA carboxylase (PCC) is a mitochondrial, biotin-dependent enzyme, 
composed of an equal number of alpha and beta subunits, that functions in the 
catabolism of branched-chain amino acids and other metabolites. Mutations of the 
PCCA (alpha subunit) or PCCB (beta subunit) gene cause the inherited metabolic 
disease, propionic acidemia. We report the cloning of a full-length cDNA 
encoding the beta subunit of human PCC. The open reading frame encodes a 
pre-beta polypeptide of 539 amino acids (58,205 Da). The cDNA was introduced 
into the expression vector, pRc/CMV, and microinjected into the nucleus or, as 
ribotranscripts, into the cytoplasm of fibroblast lines from patients with 
defects of the beta subunit. The restoration of function was monitored by 
autoradiography of PCC-dependent [14C]-propionate incorporation into cellular 
protein. These results confirm the completeness of the clone and demonstrate the 
capacity for beta subunits derived from the microinjected cDNA or RNA to be 
transported into mitochondria and assembled with endogenously derived alpha 
subunits to form functional PCC.