title: Nonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia.
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.
authors.affiliation: Department of Biology, University Tor Vergata, Roma, Italy.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chatr-Aryamontri
authors.forename: Mara
authors.initials: M
authors.lastname: Angelini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Garelli
authors.forename: Gil
authors.initials: G
authors.lastname: Tchernia
authors.forename: Ugo
authors.initials: U
authors.lastname: Ramenghi
authors.forename: Irma
authors.initials: I
authors.lastname: Dianzani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loreni
mesh_terms: D000483:Alleles; D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D018388:Codon, Terminator / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D017353:Gene Deletion; D006801:Humans; D009154:Mutation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018388:Codon, Terminator; D018076:DNA, Complementary; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C040343:ribosomal protein S19