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The genomic analysis of erythrocyte microRNA expression in sickle cell diseases.

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482.0 Kb
Date
2008-06-04
Authors
Chen, Shao-Yin
Wang, Yulei
Telen, Marilyn J
Chi, Jen-Tsan
Repository Usage Stats
416
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4
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Abstract
BACKGROUND: Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commonly thought that they do not contain nucleic acids. In this study, we have re-examined this issue by analyzing the transcriptome of a purified population of human mature erythrocytes from individuals with normal hemoglobin (HbAA) and homozygous sickle cell disease (HbSS). METHODS AND FINDINGS: Using a combination of microarray analysis, real-time RT-PCR and Northern blots, we found that mature erythrocytes, while lacking ribosomal and large-sized RNAs, contain abundant and diverse microRNAs. MicroRNA expression of erythrocytes was different from that of reticulocytes and leukocytes, and contributed the majority of the microRNA expression in whole blood. When we used microRNA microarrays to analyze erythrocytes from HbAA and HbSS individuals, we noted a dramatic difference in their microRNA expression pattern. We found that miR-320 played an important role for the down-regulation of its target gene, CD71 during reticulocyte terminal differentiation. Further investigation revealed that poor expression of miR-320 in HbSS cells was associated with their defective downregulation CD71 during terminal differentiation. CONCLUSIONS: In summary, we have discovered significant microRNA expression in human mature erythrocytes, which is dramatically altered in HbSS erythrocytes and their defect in terminal differentiation. Thus, the global analysis of microRNA expression in circulating erythrocytes can provide mechanistic insights into the disease phenotypes of erythrocyte diseases.
Type
Journal article
Subject
Anemia, Sickle Cell
Antigens, CD
Base Sequence
Blotting, Northern
DNA Primers
Erythrocytes
Gene Expression Profiling
Genomics
Hemoglobin, Sickle
Humans
MicroRNAs
Oligonucleotide Array Sequence Analysis
Phenotype
Receptors, Transferrin
Reverse Transcriptase Polymerase Chain Reaction
Permalink
https://hdl.handle.net/10161/4495
Published Version (Please cite this version)
10.1371/journal.pone.0002360
Publication Info
Chen, Shao-Yin; Wang, Yulei; Telen, Marilyn J; & Chi, Jen-Tsan (2008). The genomic analysis of erythrocyte microRNA expression in sickle cell diseases. PLoS One, 3(6). pp. e2360. 10.1371/journal.pone.0002360. Retrieved from https://hdl.handle.net/10161/4495.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Chi

Jen-Tsan Ashley Chi

Associate Professor in Molecular Genetics and Microbiology
We are using functional genomic approaches to investigate the nutrient signaling and stress adaptations of cancer cells when exposed to various nutrient deprivations and microenvironmental stress conditions. Recently, we focus on two areas. First, we are elucidating the genetic determinants and disease relevance of ferroptosis, a newly recognized form of cell death. Second, we have identified the mammalian stringent response pathway which is highly similar to bacterial stringent response, but
Telen

Marilyn Jo Telen

Wellcome Clinical Distinguished Professor of Medicine in Honor of R. Wayne Rundles, M.D.
Dr. Telen is recognized as an expert in the biochemistry and molecular genetics of blood group antigens and the pathophysiological mechanisms of vaso-occlusion in sickle cell disease. She is the Director of the Duke Comprehensive Sickle Cell Center. Dr. Telen's laboratory focuses on structure/function analysis of membrane proteins expressed by erythroid cells, as well as the role of these proteins in non-erythroid cells. Proteins are also studied in transfectant systems, and re
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