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

Shan Qing Gu, Baskar Bakthavachalu, Joonhee Han, Deepak P. Patil, Yuichi Otsuka, Chittibabu Guda, Daniel R. Schoenberg

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The PMR1 endonuclease was discovered in Xenopus liver and identified as a member of the large and diverse peroxidase gene family. The peroxidase genes arose from multiple duplication and rearrangement events, and their high degree of sequence similarity confounded attempts to identify human PMR1. The functioning of PMR1 in mRNA decay depends on the phosphorylation of a tyrosine in the C-terminal polysome targeting domain by c-Src. The sequences of regions that are required for c-Src binding and phosphorylation of Xenopus PMR1 were used to inform a bioinformatics search that identified two related genes as potential candidates for human PMR1: peroxidasin homolog (PXDN) and peroxidasin homolog-like (PXDNL) protein. Although each of these genes is predicted to encode a large, multidomain membrane-bound peroxidase, alternative splicing of PXDNL pre-mRNA yields a transcript whose predicted product is a 57-kDa protein with 42% sequence identity to Xenopus PMR1. Results presented here confirm the existence of the predicted 57-kDa protein, show this is the only form of PXDNL detected in any of the human cell lines examined, and confirm its identity as human PMR1. Like the Xenopus protein, human PMR1 binds to c-Src, is tyrosine phosphorylated, sediments on polysomes, and catalyzes the selective decay of a PMR1 substrate mRNA. Importantly, the expression of human PMR1 stimulates cell motility in a manner similar to that of the Xenopus PMR1 expressed in human cells, thus providing definitive evidence linking endonuclease decay to the regulation of cell motility. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)1186-1196
Number of pages11
JournalRNA
Volume18
Issue number6
DOIs
StatePublished - Jun 1 2012

Fingerprint

Forensic Anthropology
Pseudogenes
Endonucleases
Messenger RNA
Xenopus
Proteins
Peroxidase
Polyribosomes
Genes
Cell Movement
Tyrosine
Phosphorylation
RNA Precursors
RNA Stability
Alternative Splicing
peroxidasin
Computational Biology
Cell Line
Membranes
Liver

Keywords

  • Cell motility
  • Endonuclease
  • PMR1
  • mRNA decay

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Identification of the human PMR1 mRNA endonuclease as an alternatively processed product of the gene for peroxidasin-like protein. / Gu, Shan Qing; Bakthavachalu, Baskar; Han, Joonhee; Patil, Deepak P.; Otsuka, Yuichi; Guda, Chittibabu; Schoenberg, Daniel R.

In: RNA, Vol. 18, No. 6, 01.06.2012, p. 1186-1196.

Research output: Contribution to journalArticle

Gu, Shan Qing ; Bakthavachalu, Baskar ; Han, Joonhee ; Patil, Deepak P. ; Otsuka, Yuichi ; Guda, Chittibabu ; Schoenberg, Daniel R. / Identification of the human PMR1 mRNA endonuclease as an alternatively processed product of the gene for peroxidasin-like protein. In: RNA. 2012 ; Vol. 18, No. 6. pp. 1186-1196.
@article{df3d991823c24429bafc8409b9e85a07,
title = "Identification of the human PMR1 mRNA endonuclease as an alternatively processed product of the gene for peroxidasin-like protein",
abstract = "The PMR1 endonuclease was discovered in Xenopus liver and identified as a member of the large and diverse peroxidase gene family. The peroxidase genes arose from multiple duplication and rearrangement events, and their high degree of sequence similarity confounded attempts to identify human PMR1. The functioning of PMR1 in mRNA decay depends on the phosphorylation of a tyrosine in the C-terminal polysome targeting domain by c-Src. The sequences of regions that are required for c-Src binding and phosphorylation of Xenopus PMR1 were used to inform a bioinformatics search that identified two related genes as potential candidates for human PMR1: peroxidasin homolog (PXDN) and peroxidasin homolog-like (PXDNL) protein. Although each of these genes is predicted to encode a large, multidomain membrane-bound peroxidase, alternative splicing of PXDNL pre-mRNA yields a transcript whose predicted product is a 57-kDa protein with 42{\%} sequence identity to Xenopus PMR1. Results presented here confirm the existence of the predicted 57-kDa protein, show this is the only form of PXDNL detected in any of the human cell lines examined, and confirm its identity as human PMR1. Like the Xenopus protein, human PMR1 binds to c-Src, is tyrosine phosphorylated, sediments on polysomes, and catalyzes the selective decay of a PMR1 substrate mRNA. Importantly, the expression of human PMR1 stimulates cell motility in a manner similar to that of the Xenopus PMR1 expressed in human cells, thus providing definitive evidence linking endonuclease decay to the regulation of cell motility. Published by Cold Spring Harbor Laboratory Press.",
keywords = "Cell motility, Endonuclease, PMR1, mRNA decay",
author = "Gu, {Shan Qing} and Baskar Bakthavachalu and Joonhee Han and Patil, {Deepak P.} and Yuichi Otsuka and Chittibabu Guda and Schoenberg, {Daniel R.}",
year = "2012",
month = "6",
day = "1",
doi = "10.1261/rna.031369.111",
language = "English (US)",
volume = "18",
pages = "1186--1196",
journal = "RNA",
issn = "1355-8382",
publisher = "Cold Spring Harbor Laboratory Press",
number = "6",

}

TY - JOUR

T1 - Identification of the human PMR1 mRNA endonuclease as an alternatively processed product of the gene for peroxidasin-like protein

AU - Gu, Shan Qing

AU - Bakthavachalu, Baskar

AU - Han, Joonhee

AU - Patil, Deepak P.

AU - Otsuka, Yuichi

AU - Guda, Chittibabu

AU - Schoenberg, Daniel R.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - The PMR1 endonuclease was discovered in Xenopus liver and identified as a member of the large and diverse peroxidase gene family. The peroxidase genes arose from multiple duplication and rearrangement events, and their high degree of sequence similarity confounded attempts to identify human PMR1. The functioning of PMR1 in mRNA decay depends on the phosphorylation of a tyrosine in the C-terminal polysome targeting domain by c-Src. The sequences of regions that are required for c-Src binding and phosphorylation of Xenopus PMR1 were used to inform a bioinformatics search that identified two related genes as potential candidates for human PMR1: peroxidasin homolog (PXDN) and peroxidasin homolog-like (PXDNL) protein. Although each of these genes is predicted to encode a large, multidomain membrane-bound peroxidase, alternative splicing of PXDNL pre-mRNA yields a transcript whose predicted product is a 57-kDa protein with 42% sequence identity to Xenopus PMR1. Results presented here confirm the existence of the predicted 57-kDa protein, show this is the only form of PXDNL detected in any of the human cell lines examined, and confirm its identity as human PMR1. Like the Xenopus protein, human PMR1 binds to c-Src, is tyrosine phosphorylated, sediments on polysomes, and catalyzes the selective decay of a PMR1 substrate mRNA. Importantly, the expression of human PMR1 stimulates cell motility in a manner similar to that of the Xenopus PMR1 expressed in human cells, thus providing definitive evidence linking endonuclease decay to the regulation of cell motility. Published by Cold Spring Harbor Laboratory Press.

AB - The PMR1 endonuclease was discovered in Xenopus liver and identified as a member of the large and diverse peroxidase gene family. The peroxidase genes arose from multiple duplication and rearrangement events, and their high degree of sequence similarity confounded attempts to identify human PMR1. The functioning of PMR1 in mRNA decay depends on the phosphorylation of a tyrosine in the C-terminal polysome targeting domain by c-Src. The sequences of regions that are required for c-Src binding and phosphorylation of Xenopus PMR1 were used to inform a bioinformatics search that identified two related genes as potential candidates for human PMR1: peroxidasin homolog (PXDN) and peroxidasin homolog-like (PXDNL) protein. Although each of these genes is predicted to encode a large, multidomain membrane-bound peroxidase, alternative splicing of PXDNL pre-mRNA yields a transcript whose predicted product is a 57-kDa protein with 42% sequence identity to Xenopus PMR1. Results presented here confirm the existence of the predicted 57-kDa protein, show this is the only form of PXDNL detected in any of the human cell lines examined, and confirm its identity as human PMR1. Like the Xenopus protein, human PMR1 binds to c-Src, is tyrosine phosphorylated, sediments on polysomes, and catalyzes the selective decay of a PMR1 substrate mRNA. Importantly, the expression of human PMR1 stimulates cell motility in a manner similar to that of the Xenopus PMR1 expressed in human cells, thus providing definitive evidence linking endonuclease decay to the regulation of cell motility. Published by Cold Spring Harbor Laboratory Press.

KW - Cell motility

KW - Endonuclease

KW - PMR1

KW - mRNA decay

UR - http://www.scopus.com/inward/record.url?scp=84861405066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861405066&partnerID=8YFLogxK

U2 - 10.1261/rna.031369.111

DO - 10.1261/rna.031369.111

M3 - Article

VL - 18

SP - 1186

EP - 1196

JO - RNA

JF - RNA

SN - 1355-8382

IS - 6

ER -