Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells.
Piwi (P-element-induced wimpy testis) first discovered in Drosophila is a member of the Argonaute family of micro-RNA binding proteins with essential roles in germ-cell development. The murine homologue of PiwiL2, also known as Mili is selectively expressed in the testes, and mice bearing targeted mutations of the PiwiL2 gene are male-sterile. PiwiL2 proteins are thought to protect the germ line genome by suppressing retrotransposons, stabilizing heterochromatin structure, and regulating target genes during meiosis and mitosis. Here, we report that PiwiL2 and associated piRNAs (piRs) may play similar roles in adult mouse mesenchymal stem cells. We found that PiwiL2 is expressed in the cytoplasm of metaphase mesenchymal stem cells from the bone marrow of adult and aged mice. Knockdown of PiwiL2 with a specific siRNA enhanced cell proliferation, significantly increased the number of cells in G1/S and G2/M cell cycle phases and was associated with increased expression of cell cycle genes CCND1, CDK8, microtubule regulation genes, and decreased expression of tumor suppressors Cables 1, LATS, and Cxxc4. The results suggest broader roles for Piwi in genome surveillance beyond the germ line and a possible role in regulating the cell cycle of mesenchymal stem cells.
Wu
Qiuling
Q
Department of Molecular and Cellular Pharmacology, Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Ma
Qi
Q
Shehadeh
Lina A
LA
Wilson
Amber
A
Xia
Linghui
L
Yu
Hong
H
Webster
Keith A
KA
D000818:Animals; D060565:Argonaute Proteins; D002352:Carrier Proteins / Q000096:biosynthesis; D002453:Cell Cycle; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis; D056850:Cyclin-Dependent Kinase 8 / Q000096:biosynthesis; D016213:Cyclins / Q000096:biosynthesis; D003593:Cytoplasm / Q000378:metabolism; D016193:G1 Phase; D016195:G2 Phase; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008938:Mitosis; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase
D060565:Argonaute Proteins; C411580:Cables1 protein, mouse; D002352:Carrier Proteins; C530105:Ccnd1 protein, mouse; D016213:Cyclins; D035683:MicroRNAs; D010750:Phosphoproteins; C448521:Piwil2 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D019938:Cyclin D1; C490501:Lats1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C524803:Cdk8 protein, mouse; D056850:Cyclin-Dependent Kinase 8
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