title: miR-570 interacts with mitochondrial ATPase subunit g (ATP5L) encoding mRNA in stored platelets.
abstract: Loss of platelet quality during ex vivo storage is a major concern in the transfusion medicine field and it has been known that platelet mitochondrial dysfunction is associated with storage time. In the last decade, small noncoding RNAs also known as microRNAs (miRNAs) have been reported to regulate key cellular processes through their target sequence interactions with selected mRNAs. In this study, we focused on understanding the mechanisms of platelet mitochondrial dysfunction during storage through miRNA regulation of mRNAs. RNA was isolated from day 0, day 5, and day 9 of stored human leukocyte-depleted platelets and subjected to differential miRNA and mRNA profiling. The miRNA profiling identified several miRNAs at low levels including a set of 12 different miR-548 family members (miR-548a-3p, miR-548aa, miR-548x, miR-548ac, miR-548c-3p, miR-603, miR-548aj, miR-548ae, miR-548z, miR-548u, miR-548al, and miR-570-3p). The mRNA profiling identified, among many, the mitochondrial ATP synthase subunit g (ATP5L) mRNA at high levels during storage. Target Scan algorithm for potential targets of miR-570-3p also identified ATP5L as one of its targets. We further identified two target sites for miR-570-3p in the 3' untranslated region (3'UTR) of ATP5L mRNA. While ATP5L is a subunit of F0ATPase complex, its function is not established yet. Overexpression of miR-570-3p in platelets resulted in reduced levels of ATP5L mRNA and concomitant ATP loss. These experimental results provide first-time insights into the miRNA-mRNA interactions underlying mitochondrial dysfunction in ex vivo stored platelets and warrants further investigation.
authors: a Section of Cell Biology, Laboratory of Cellular Hematology, Division of Hematology, Center for Biologics Evaluation and Research, US Food and Drug Administration , Silver Spring , MD , USA.
authors: Neetu
authors: N
authors: Dahiya
authors: a Section of Cell Biology, Laboratory of Cellular Hematology, Division of Hematology, Center for Biologics Evaluation and Research, US Food and Drug Administration , Silver Spring , MD , USA.|b Department of Clinical Chemistry, Faculty of Allied Health Sciences , Chulalongkorn University , Bangkok , Thailand.
authors: Tewarit
authors: T
authors: Sarachana
authors: a Section of Cell Biology, Laboratory of Cellular Hematology, Division of Hematology, Center for Biologics Evaluation and Research, US Food and Drug Administration , Silver Spring , MD , USA.
authors: Sandhya
authors: S
authors: Kulkarni
authors: c Laboratory of Genetics, National Institute on Aging , Baltimore , MD , USA.
authors: William H
authors: WH
authors: Wood
authors: c Laboratory of Genetics, National Institute on Aging , Baltimore , MD , USA.
authors: Yongqing
authors: Y
authors: Zhang
authors: c Laboratory of Genetics, National Institute on Aging , Baltimore , MD , USA.
authors: Kevin G
authors: KG
authors: Becker
authors: d Department of Pharmacology and Physiology , The George Washington School of Medicine and Health Sciences , Washington , DC , USA.
authors: Bi-Dar
authors: BD
authors: Wang
authors: a Section of Cell Biology, Laboratory of Cellular Hematology, Division of Hematology, Center for Biologics Evaluation and Research, US Food and Drug Administration , Silver Spring , MD , USA.
authors: Chintamani D
authors: CD
authors: Atreya
mesh_terms: D020413:3' Untranslated Regions; D000251:Adenosine Triphosphatases / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D001793:Blood Preservation; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C582115:MIRN570 microRNA, human; D035683:MicroRNAs; D021122:Protein Subunits; D012333:RNA, Messenger; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases
keywords: ATP5L; microRNA; microarray; platelets; storage lesion