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: Wannapa Sornjai, Pathrapol Lithanatudom, Jenny Erales, Philippe Joly, Alain Francina, Sabine Hacot, Suthat Fucharoen, Saovaros Svasti, Jean Jacques Diaz, Hichem C Mertani, Duncan R Smith
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 94 Issue Pt A Pg. 728-734 (Jan 2017) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 27765567 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Chromosomal Proteins, Non-Histone
• RNA, Ribosomal, 28S
• RNA, Small Nucleolar
• fibrillarin
• pseudouridylic acid
• Hemoglobin E
• Uridine Monophosphate

Topics

• Case-Control Studies
• Chromosomal Proteins, Non-Histone (genetics, metabolism)
• Gene Expression
• Hematopoietic Stem Cells (metabolism, pathology)
• Hemoglobin E (genetics, metabolism)
• Heterozygote
• Humans
• Leukocytes, Mononuclear (metabolism, pathology)
• Methylation
• Primary Cell Culture
• Protein Biosynthesis
• RNA Processing, Post-Transcriptional
• RNA, Ribosomal, 28S (genetics, metabolism)
• RNA, Small Nucleolar (genetics, metabolism)
• Ribosomes (genetics, metabolism)
• Uridine Monophosphate (genetics, metabolism)
• beta-Thalassemia (genetics, metabolism, pathology)