The Identification and Genomic Analysis of microRNAs in Human Erythrocytes in Sickle Cell Diseases.

Erythrocytes are circulating blood cells responsible for efficient gas exchange in human body. 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 re-examined this issue and found that human mature erythrocytes, while lacking ribosomal and large-sized RNAs, possess abundant small-sized RNAs. Using a combination of microarray analysis, real-time RT-PCR and Northern blots we found that mature erythrocytes contained abundant and diverse microRNAs which were distinct from microRNAs observed in reticulocytes/leukocytes and contributed to the majority of the microRNA expression in whole blood. When we used microarrays to analyze erythrocytes from normal (HbAA) and homozygous sickle (HbSS) individulas, we noted dramatic a difference in their microRNA expression pattern. To investigate how this difference is associated with erythrocyte disease phenotypes, we found that the poor expression of miR-320 was responsible for the defective downregulation of its target gene CD71 in HbSS cells during terminal differentiation. Collectively, we have discovered significant microRNA expression in human mature erythrocytes, which enables the microarray analysis of erythrocyte property to provide insights into the human erythrocyte diseases.