Published on Jan. 1, 2017 in Int J Biol Macromol volume 94(Pt A).

PubMed ID: 27765567

DOI: S0141-8130(16)31101-1

Abstract:

Ribosome biogenesis is the process of synthesis of the cellular ribosomes whichmediate protein translation. Integral with the ribosomes are four cytoplasmicribosomal RNAs (rRNAs) which show extensive post-transcriptional modificationsincluding 2'-O-methylation and pseudouridylation. Several hereditary hematologicdiseases including Diamond-Blackfan anemia have been shown to be associated withdefects in ribosome biogenesis. Thalassemia is the most important hematologicinherited genetic disease worldwide, and this study examined thepost-transcriptional ribose methylation status of three specific active sites of the28S rRNA molecule at positions 1858, 4197 and 4506 of β-thalassemia trait carriersand normal controls. Samples from whole blood and cultured erythroid cells wereexamined. Results showed that site 4506 was hypermethylated in β-thalassemia traitcarriers in both cohorts. Expression of fibrillarin, the ribosomal RNAmethyltransferase as well as snoRNAs were additionally quantified by RT-qPCR andevidence of dysregulation was seen. Hemoglobin E trait carriers also showed evidenceof dysregulation. These results provide the first evidence that ribosome biogenesisis dysregulated in β-thalassemia trait carriers.CI - Copyright © 2016 Elsevier B.V. All rights reserved.