| Affiliation: | (1) Department of Biomolecular Chemistry, Nijmegen Centre for Molecular Life Sciences, Institute for Molecules and Materials, Radboud University Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands;(2) Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520-8011, USA;(3) Children’s Hospital, University of Mainz, 55101 Mainz, Germany;(4) Department of Pediatrics, Centre for Pediatrics and Adolescent Medicine, Freiburg University Hospital, 79106 Freiburg, Germany |
| 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. |
