Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease

Sandy Mattijssen; Ella R Hinson; Carla Onnekink; Pia Hermanns; Bernhard Zabel; Peter Cresswell; Ger J M Pruijn

doi:10.1007/s00018-010-0568-3

Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease

Cell Mol Life Sci. 2011 Jul;68(14):2469-80. doi: 10.1007/s00018-010-0568-3. Epub 2010 Oct 30.

Authors

Sandy Mattijssen¹, Ella R Hinson, Carla Onnekink, Pia Hermanns, Bernhard Zabel, Peter Cresswell, Ger J M Pruijn

Affiliation

¹ Department of Biomolecular Chemistry, Nijmegen Centre for Molecular Life Sciences, Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands. s.mattijssen@ncmls.ru.nl

Abstract

RNase MRP is a conserved endoribonuclease, in humans consisting of a 267-nucleotide RNA associated with 7-10 proteins. Mutations in its RNA component lead to several autosomal recessive skeletal dysplasias, including cartilage-hair hypoplasia (CHH). Because the known substrates of mammalian RNase MRP, pre-ribosomal RNA, and RNA involved in mitochondrial DNA replication are not likely involved in CHH, we analyzed the effects of RNase MRP (and the structurally related RNase P) depletion on mRNAs using DNA microarrays. We confirmed the upregulation of the interferon-inducible viperin mRNA by RNAi experiments and this appeared to be independent of the interferon response. We detected two cleavage sites for RNase MRP/RNase P in the coding sequence of viperin mRNA. This is the first study providing direct evidence for the cleavage of a mRNA by RNase MRP/RNase P in human cells. Implications for the involvement in the pathophysiology of CHH are discussed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism
Binding Sites / genetics
Blotting, Northern
Cell Line, Tumor
Endoribonucleases / genetics
Endoribonucleases / metabolism*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects
Hair / abnormalities
Hair / metabolism
HeLa Cells
Hirschsprung Disease / genetics
Hirschsprung Disease / metabolism
Humans
Immunoblotting
Immunologic Deficiency Syndromes / genetics
Immunologic Deficiency Syndromes / metabolism
Interferon-alpha / pharmacology
Oligonucleotide Array Sequence Analysis
Osteochondrodysplasias / congenital
Osteochondrodysplasias / genetics
Osteochondrodysplasias / metabolism
Oxidoreductases Acting on CH-CH Group Donors
Primary Immunodeficiency Diseases
Proteins / genetics*
RNA Interference
RNA, Messenger / genetics
RNA, Messenger / metabolism*
Ribonuclease P / genetics
Ribonuclease P / metabolism*
Ribonucleoproteins / genetics
Ribonucleoproteins / metabolism

Substances

Apoptosis Regulatory Proteins
Interferon-alpha
POP1 protein, human
Proteins
RNA, Messenger
Ribonucleoproteins
Oxidoreductases Acting on CH-CH Group Donors
RSAD2 protein, human
Endoribonucleases
mitochondrial RNA-processing endoribonuclease
RPP40 protein, human
Ribonuclease P

Supplementary concepts

Cartilage-hair hypoplasia