Expression of the gene for mitoribosomal protein S12 is controlled in human cells at the levels of transcription, RNA splicing, and translation

The human gene RPMS12 encodes a protein similar to bacterial ribosomal prot ein S12 and is proposed to represent the human mitochondrial orthologue, RP MS12 reporter gene expression in cultured human cells supports the idea tha t the gene product is mitochondrial and is localized to the inner membrane. Human cells contain at least four structurally distinct RPMS12 mRNAs that differ in their 5'-untranslated region (5'-UTR) as a result of alternate sp licing and of 5' end heterogeneity. All of them encode the same polypeptide , The full 5'-UTR contains two types of sequence element implicated elsewhe re in translational regulation as follows: a short upstream open reading fr ame and an oligopyrimidine tract similar to that found at the 5' end of mRN As encoding other growth-regulated proteins, including those of cytosolic r ibosomes, The fully spliced (short) mRNA is the predominant form in all cel l types studied and is translationally down-regulated in cultured cells in response to serum starvation, even though it lacks both of the putative tra nslational regulatory elements. By contrast, other splice variants containi ng one or both of these elements are not translationally regulated by growt h status but are translated poorly in both growing and non-growing cells. R eporter analysis identified a 26-nucleotide tract of the 5'-UTR of the shor t mRNA that is essential for translational down-regulation in growth-inhibi ted cells. Such experiments also confirmed that the 5'-UTR of the longer mR NA variants contains negative regulatory elements for translation. Tissue r epresentation of RPMS12 mRNA is highly variable, following a typical mitoch ondrial pattern, but the relative levels of the different splice variants a re similar in different tissues. These findings indicate a complex, multile vel regulation of RPMS12 gene expression in response to signals mediating g rowth, tissue specialization, and probably metabolic needs.