Mutations in the ribosomal protein (RP)S19 gene have been found in about 25% of the cases of Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia that includes variable physical malformations. Various mutations have been identified in the RPS19 gene, but no investigations regarding the effect of these alterations on RPS19 mRNA levels have been performed. It is well established that mutated mRNA containing a premature stop codon (PTC) or lacking a stop codon can be rapidly degraded by specific mechanisms called nonsense mediated decay (NMD) and nonstop decay. To study the involvement of such mechanisms in DBA, we analyzed immortalized lymphoblastoid cells and primary fibroblasts from patients presenting different kinds of mutations in the RPS19 gene, generating allelic deletion, missense, nonsense, and nonstop messengers. We found that RPS19 mRNA levels are decreased in the cells with allelic deletion and, to a variable extent, also in all the cell lines with PTC or nonstop mutations. Further analysis showed that translation inhibition causes a stabilization of the mutated RPS19 mRNA. Our findings indicate that NMD and nonstop decay affect the expression of mutated RPS19 genes; this may help to clarify genotype-phenotype correlations in DBA. © 2004 Wiley-Liss, Inc.

Chatr Aryamontri, A., Angelini, M., Garelli, E., Tchernia, G., Ramenghi, U., Dianzani, I., et al. (2004). Nonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia. HUMAN MUTATION, 24(6), 526-533 [10.1002/humu.20117].

Nonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia

LORENI, FABRIZIO
2004-01-01

Abstract

Mutations in the ribosomal protein (RP)S19 gene have been found in about 25% of the cases of Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia that includes variable physical malformations. Various mutations have been identified in the RPS19 gene, but no investigations regarding the effect of these alterations on RPS19 mRNA levels have been performed. It is well established that mutated mRNA containing a premature stop codon (PTC) or lacking a stop codon can be rapidly degraded by specific mechanisms called nonsense mediated decay (NMD) and nonstop decay. To study the involvement of such mechanisms in DBA, we analyzed immortalized lymphoblastoid cells and primary fibroblasts from patients presenting different kinds of mutations in the RPS19 gene, generating allelic deletion, missense, nonsense, and nonstop messengers. We found that RPS19 mRNA levels are decreased in the cells with allelic deletion and, to a variable extent, also in all the cell lines with PTC or nonstop mutations. Further analysis showed that translation inhibition causes a stabilization of the mutated RPS19 mRNA. Our findings indicate that NMD and nonstop decay affect the expression of mutated RPS19 genes; this may help to clarify genotype-phenotype correlations in DBA. © 2004 Wiley-Liss, Inc.
2004
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Con Impact Factor ISI
messenger RNA; protein s19; ribosome protein; unclassified drug; allele; article; Blackfan Diamond anemia; congenital hypoplastic anemia; congenital malformation; controlled study; fibroblast; gene deletion; gene expression regulation; gene identification; gene mutation; genetic stability; human; human cell; lymphoblastoid cell; missense mutation; nonsense mediated decay; nonsense mutation; nonstop decay; nucleotide sequence; priority journal; protein analysis; rare disease; regulatory mechanism; RNA analysis; RNA degradation; stop codon; Alleles; Anemia, Diamond-Blackfan; Blotting, Northern; Cell Line; Cells, Cultured; Codon, Terminator; DNA Mutational Analysis; DNA, Complementary; Gene Deletion; Humans; Mutation; Protein Biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal Proteins; RNA, Messenger; Sequence Analysis, DNA
Chatr Aryamontri, A., Angelini, M., Garelli, E., Tchernia, G., Ramenghi, U., Dianzani, I., et al. (2004). Nonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia. HUMAN MUTATION, 24(6), 526-533 [10.1002/humu.20117].
Chatr Aryamontri, A; Angelini, M; Garelli, E; Tchernia, G; Ramenghi, U; Dianzani, I; Loreni, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/25372
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