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J Biol Chem, Vol. 274, Issue 45, 31853-31862, November 5, 1999
From the The human gene RPMS12 encodes a
protein similar to bacterial ribosomal protein S12 and is proposed to
represent the human mitochondrial orthologue. RPMS12
reporter gene expression in cultured human cells supports the idea that
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 splicing and of 5' end
heterogeneity. All of them encode the same polypeptide. The full 5'-UTR
contains two types of sequence element implicated elsewhere in
translational regulation as follows: a short upstream open reading
frame and an oligopyrimidine tract similar to that found at the 5' end
of mRNAs encoding other growth-regulated proteins, including those
of cytosolic ribosomes. The fully spliced (short) mRNA is the
predominant form in all cell types studied and is translationally
down-regulated in cultured cells in response to serum starvation, even
though it lacks both of the putative translational regulatory elements.
By contrast, other splice variants containing one or both of these
elements are not translationally regulated by growth status but are
translated poorly in both growing and non-growing cells. Reporter
analysis identified a 26-nucleotide tract of the 5'-UTR of the short
mRNA that is essential for translational down-regulation in
growth-inhibited cells. Such experiments also confirmed that the 5'-UTR
of the longer mRNA variants contains negative regulatory elements
for translation. Tissue representation of RPMS12 mRNA
is highly variable, following a typical mitochondrial pattern, but the
relative levels of the different splice variants are similar in
different tissues. These findings indicate a complex, multilevel
regulation of RPMS12 gene expression in response to signals
mediating growth, tissue specialization, and probably metabolic needs.
Expression of the Gene for Mitoribosomal Protein S12 Is
Controlled in Human Cells at the Levels of Transcription, RNA
Splicing, and Translation
,
Department of Biology, Universitá di
"Roma Tre," Rome, I-00146, Italy, the § Institute of
Medical Technology and Tampere University Hospital, University of
Tampere, Tampere, Fin-33101, Finland, the ¶ Department of
Biology, Universitá di Roma "Tor Vergata,"
Rome, I-00133, Italy, and the
Institute of Biomedical and Life
Sciences, University of Glasgow,
Glasgow, G12 8QQ, Scotland, United Kingdom
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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