Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease.
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.
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
Sandy
S
Mattijssen
Ella R
ER
Hinson
Carla
C
Onnekink
Pia
P
Hermanns
Bernhard
B
Zabel
Peter
P
Cresswell
Ger J M
GJ
Pruijn
D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006197:Hair / Q000002:abnormalities / Q000378:metabolism; D006367:HeLa Cells; D006627:Hirschsprung Disease / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010009:Osteochondrodysplasias / Q000151:congenital / Q000235:genetics / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000081207:Primary Immunodeficiency Diseases; D011506:Proteins / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D043262:Ribonuclease P / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D000090123:Viperin Protein
D051017:Apoptosis Regulatory Proteins; D004722:Endoribonucleases; D016898:Interferon-alpha; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; D012333:RNA, Messenger; D043262:Ribonuclease P; D012261:Ribonucleoproteins; C490350:POP1 protein, human; C444427:RSAD2 protein, human; D000090123:Viperin Protein; C058330:mitochondrial RNA-processing endoribonuclease; C112707:RPP40 protein, human