title: Hypermethylation of 28S ribosomal RNA in β-thalassemia trait carriers.
abstract: Ribosome biogenesis is the process of synthesis of the cellular ribosomes which mediate protein translation. Integral with the ribosomes are four cytoplasmic ribosomal RNAs (rRNAs) which show extensive post-transcriptional modifications including 2'-O-methylation and pseudouridylation. Several hereditary hematologic diseases including Diamond-Blackfan anemia have been shown to be associated with defects in ribosome biogenesis. Thalassemia is the most important hematologic inherited genetic disease worldwide, and this study examined the post-transcriptional ribose methylation status of three specific active sites of the 28S rRNA molecule at positions 1858, 4197 and 4506 of β-thalassemia trait carriers and normal controls. Samples from whole blood and cultured erythroid cells were examined. Results showed that site 4506 was hypermethylated in β-thalassemia trait carriers in both cohorts. Expression of fibrillarin, the ribosomal RNA methyltransferase as well as snoRNAs were additionally quantified by RT-qPCR and evidence of dysregulation was seen. Hemoglobin E trait carriers also showed evidence of dysregulation. These results provide the first evidence that ribosome biogenesis is dysregulated in β-thalassemia trait carriers.
authors.affiliation: Institute of Molecular Bioscience, Mahidol University, Thailand.
authors.forename: Wannapa
authors.initials: W
authors.lastname: Sornjai
authors.affiliation: Institute of Molecular Bioscience, Mahidol University, Thailand; Department of Biology, Faculty of Science, Chiang Mai University, Thailand.
authors.forename: Pathrapol
authors.initials: P
authors.lastname: Lithanatudom
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052-CNRS 5286, Centre Léon Bérard, Université de Lyon, Lyon, France.
authors.forename: Jenny
authors.initials: J
authors.lastname: Erales
authors.affiliation: Unité de Pathologie Moléculaire du Globule Rouge, Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
authors.affiliation: Unité de Pathologie Moléculaire du Globule Rouge, Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Francina
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052-CNRS 5286, Centre Léon Bérard, Université de Lyon, Lyon, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hacot
authors.affiliation: Institute of Molecular Bioscience, Mahidol University, Thailand.
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.affiliation: Institute of Molecular Bioscience, Mahidol University, Thailand.
authors.forename: Saovaros
authors.initials: S
authors.lastname: Svasti
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052-CNRS 5286, Centre Léon Bérard, Université de Lyon, Lyon, France.
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Diaz
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052-CNRS 5286, Centre Léon Bérard, Université de Lyon, Lyon, France. Electronic address: hichem.mertani@lyon.unicancer.fr.
authors.forename: Hichem C
authors.initials: HC
authors.lastname: Mertani
authors.affiliation: Institute of Molecular Bioscience, Mahidol University, Thailand. Electronic address: duncan_r_smith@hotmail.com.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D016022:Case-Control Studies; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006446:Hemoglobin E / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008745:Methylation; D061251:Primary Cell Culture; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012339:RNA, Ribosomal, 28S / Q000235:genetics / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D014542:Uridine Monophosphate / Q000235:genetics / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D012339:RNA, Ribosomal, 28S; D020537:RNA, Small Nucleolar; C047458:fibrillarin; C100044:pseudouridylic acid; D006446:Hemoglobin E; D014542:Uridine Monophosphate
keywords: Fibrillarin; Ribosome biogenesis; rRNA methylation; β-Thalassemia