Fol. Biol. 2002, 48, 182-191
Cloning and Expression of PARP-3 (Adprt3) and U3-55k, Two Genes Closely Linked on Mouse Chromosome 9
Post-translational modification of nuclear proteins by poly(ADP-ribose) polymerase 1 (PARP-1) is involved in the regulation of DNA repair, cell death, and maintenance of genomic stability. Recently, several PARP-1 homologues have been identified constituting a family of poly(ADP-ribosylating proteins. We cloned and sequenced the CDNAs of the mouse PARP-3 (Adprt3) gene encoding poly(ADP-ribose) polymerase 3 and of the closely linked U3-55k gene coding for the U3 small nucleolar ribonucleoprotein complex-associated 55-kilodalton protein. The two genes are located in a head-to-head orientation on mouse chromosome 9 and are linked by an approximately 1.5-kb putative bi-directional promoter region. This gene arrangement is conserved between mouse and human orthologues. Three alternative non-coding 5'-end exons were found in the mouse PARP-3 mRNA. The expression patterns of PARP-3, U3-55k, PARP-2, and PARP-1 genes were determined using Northern blot with mRNA from various adult mouse tissues and organs. PARP-3 expression was found to be regulated in a tissue-specific manner. The highest expression of PARP-3 was detected in the skeletal muscle, high to moderate levels were found in the lung, liver, kidney, ovary, spleen and heart, while thymus, small intestine and colon contained lower levels of the PARP-3 transcripts. Notably, PARP-3 expression was barely detectable in the whole brain and testis mRNA. In contrast to PARP-3, the other three genes showed ubiquitous expression with less variable mRNA levels. Interestingly, the mouse and human PARP-2 gene has recently been shown to be connected via a bi-directional promoter with the gene for the RNase P RNA subunit (Amé et al., J. Biol. Chem. 276: 11092-11099, 2001). As both the U3-55k protein and the RNase P RNA are involved in the processing of precursor RNAs of the protein-synthesizing machinery (pre-RNA and pre-tRNA, respectively), it is tempting to hypothesize that expression of some members of the two groups of genes (i.e. PARP vs. protein-synthesizing machinery RNA-processing genes) may be coordinately regulated under certain physiological or pathological conditions and/or in some cell types.
Keywords
poly(ADP-ribose) polymerase, PARP, Adprt, ADPRTL, PARP-1, PARP-2, hU3-55k, Rrp9p, U3 snoRNA, U3 snoRNP, WD-repeat protein, bi-directional promoter, tissue-specific gene expression, orthologue.
Funding
This work was supported by the Grant Agency of the Academy of Sciences of the Czech Republic, grant No. A5052802, and in part by the Center for Integrated Genomics and by the Grant Agency of the Czech Republic, grant No. 204/00/0554.
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.