Hypermethylation of 28S ribosomal RNA in β-thalassemia trait carriers

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• 作者：Wannapa Sornjai^a ; ¹ ; Pathrapol Lithanatudom^a ; ^b ; ¹ ; Jenny Erales^c ; Philippe Joly^d ; Alain Francina^d ; Sabine Hacot^c ; Suthat Fucharoen^a ; Saovaros Svasti^a ; Jean Jacques Diaz^c ; Hichem C. Mertani ; PhD^c ; ² ; ^{hichem.mertani@lyon.unicancer.fr} ; Duncan R. Smith ; PhD^a ; ² ; ^{duncan_r_smith@hotmail.com}
• 关键词：Fibrillarin ; Ribosome biogenesis ; β-Thalassemia ; rRNA methylation
• 刊名：International Journal of Biological Macromolecules
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：94
• 期：part_PA
• 页码：728-734
• 全文大小：724 K
• 卷排序：94

文摘

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.