Talk abstracts

Talk on Friday 03:30-03:45pm submitted by Shan-Qing Gu

Identification of the human PMR1 mRNA endonuclease as an alternatively processed product of the gene for peroxidasin-like protein

Shan-Qing Gu (Center for RNA Biology and Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210-1218 ), Baskar Bakthavachalu, Joonhee Han, Deepak Patil, Yuichi Otsuka (Center for RNA Biology and Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210-1218 ), Chittibabu Guda (Center for Bioinformatics and Systems Biology, Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68118-5145), Daniel R. Schoenberg (Center for RNA Biology and Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210-1218 )

Abstract:
PMR1 is an mRNA endonuclease that degrades its targets while they are engaged by translating ribosomes. To date all of the work on this enzyme has been done on the Xenopus protein because of difficulties in identifying an obvious human ortholog. Xenopus PMR1 is an alternatively processed form of eosinophil peroxidase gene, but there is no evidence for a similar protein from this or any of the other human peroxidase genes. Results in this study identify the newly discovered gene for peroxidasin-like protein as the source of human PMR1. The two peroxidasin genes are a subgroup of the large peroxidase gene family. Both encode a 164 kDa membrane-bound protein with a heme peroxidase domain. In addition peroxidasin-like protein undergoes alternative splicing, the predicted product of which is a 57 kDa protein that shares critical features of Xenopus PMR1, including active site histidines, c-Src binding site, tyrosine phosphorylation site and SH2 binding site. We show here that this is the major form of peroxidasin-like protein in a number of cell lines, and using criteria developed in the course of characterizing the Xenopus protein demonstrate that this is human PMR1.

Keywords: mRNA decay, PMR1, RNA endonuclease