title: Mature Let-7 miRNAs fine tune expression of LIN28B in pluripotent human embryonic stem cells.
abstract: MicroRNAs (miRNA) are central regulators of diverse biological processes and are important in the regulation of stem cell self-renewal. One of the widely studied miRNA-protein regulators is the Lin28-Let-7 pair. In this study, we demonstrate that contrary to the well-established models of mouse ES cells (mESC) and transformed human cancer cells, the pluripotent state of human ES cells (hESC) involves expression of mature Let-7 family miRNAs with concurrent expression of all LIN28 proteins. We show that mature Let-7 miRNAs are regulated during hESC differentiation and have opposite expression profile with LIN28B. Moreover, mature Let-7 miRNAs fine tune the expression levels of LIN28B protein in pluripotent hESCs, whereas silencing of LIN28 proteins have no effect on mature Let-7 levels. These results bring novel information to the highly complex network of human pluripotency and suggest that maintenance of hESC pluripotency differs greatly from the mESCs in regard to LIN28-Let-7 regulation.
authors: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland. Electronic address: nelly.rahkonen@ki.se.
authors: Nelly
authors: N
authors: Rahkonen
authors: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
authors: Aki
authors: A
authors: Stubb
authors: Department of Information and Computer Science, Aalto University, Espoo 00076, Finland.
authors: Maia
authors: M
authors: Malonzo
authors: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
authors: Sanna
authors: S
authors: Edelman
authors: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
authors: Maheswara Reddy
authors: MR
authors: Emani
authors: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
authors: Elisa
authors: E
authors: Närvä
authors: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland; Department of Information and Computer Science, Aalto University, Espoo 00076, Finland.
authors: Harri
authors: H
authors: Lähdesmäki
authors: Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA.
authors: Hannele
authors: H
authors: Ruohola-Baker
authors: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
authors: Riitta
authors: R
authors: Lahesmaa
authors: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.
authors: Riikka
authors: R
authors: Lund
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000066449:Human Embryonic Stem Cells / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human
keywords: Human embryonic stem cell; LIN28; Let-7; Pluripotency