MicroRNAs 10a and 10b Regulate the Expression of Human Platelet Glycoprotein Ibα for Normal Megakaryopoiesis.
MicroRNAs are a class of small non-coding RNAs that bind to the three prime untranslated region (3'-UTR) of target mRNAs. They cause a cleavage or an inhibition of the translation of target mRNAs, thus regulating gene expression. Here, we employed three prediction tools to search for potential miRNA target sites in the 3'-UTR of the human platelet glycoprotein (GP)1BAgene. A luciferase reporter assay shows that miR-10a and -10b sites are functional. When miR-10a or -10b mimics were transfected into the GP Ibβ/GP IX-expressing cells, along with a DNA construct harboring both the coding and 3'-UTR sequences of the humanGP1BAgene, we found that they inhibit the transient expression of GP Ibα on the cell surface. When the miR-10a or -10b mimics were introduced into murine progenitor cells, upon megakaryocyte differentiation, we found that GP Ibα mRNA expression was markedly reduced, suggesting that a miRNA-induced mRNA degradation is at work. Thus, our study identifies GP Ibα as a novel target of miR-10a and -10b, suggesting that a drastic reduction in the levels of miR-10a and -10b in the late stage of megakaryopoiesis is required to allow the expression of human GP Ibα and the formation of the GP Ib-IX-V complex.
School of Basic Medicine, Central South University, Changsha 410013, China. zhangzuping@csu.edu.cn.|Cardiovascular Research Section, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. zhangzuping@csu.edu.cn.
Zuping
Z
Zhang
Cardiovascular Research Section, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Ran_yali@163.com.
Yali
Y
Ran
Cardiovascular Research Section, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. tshaw@bcm.edu.
Tanner S
TS
Shaw
Cardiovascular Research Section, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Yuandong@bcm.edu.
Yuandong
Y
Peng
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003412:Cricetulus; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D034061:Thrombopoiesis / Q000235:genetics*
D020413:3' Untranslated Regions; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D008156:Luciferases
gene regulation; microRNA; platelet glycoprotein Ibα