title: Novel glycylated sugar alcohols protect ESC-specific microRNAs from degradation in iPS cells.
abstract: Excessive accumulation of embryonic stem cell (ESC)-specific microRNAs occurs in both ESCs and induced pluripotent stem cells (iPSC); yet, the mechanism involved is unknown. In iPSCs, we for the first time found that novel glycylated sugar alcohols, particularly glycylglycerins, are tightly bound with ESC-specific microRNA precursors (pre-miRNA), such as pre-miR-302. Among these isolated glycylglycerins, we further identified that 1,3-diglycylglycerin and 1,2,3-triglycylglycerin are two major compounds bonded with negatively charged nucleic acids via electro-affinity and subsequently forming sugar-like coats in the hairpin-like double helix structures of pre-miRNAs. As a result, such glycylglycerin-formed coating serves as a protection layer against miRNA degradation. Moreover, we found that the pH value of iPSC cytosol determines the charges of these glycylglycerins. During iPSC differentiation, the cytosol pH is increased and hence neutralizes the charges of glycylglycerins, consequently leading to fast miRNA degradation. Therefore, the current findings not only explain how ESC-specific miRNAs are preserved and accumulated in iPSCs and ESCs but also demonstrate an important function of glycylglycerins in protecting the structural integrity of highly degradable miRNAs, providing a useful means for maintaining miRNA/siRNA function as well as developing the related RNA interference (RNAi) applications.
authors.affiliation: WJWU & LYNN Institute for Stem Cell Research, 12145 Mora Drive, Santa Fe Springs, CA 90670, USA Department of Cell & Neurobiology, Keck School of Medicine, University of Southern California, CA 90033, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Chang-Lin
authors.affiliation: WJWU & LYNN Institute for Stem Cell Research, 12145 Mora Drive, Santa Fe Springs, CA 90670, USA Department of Cell & Neurobiology, Keck School of Medicine, University of Southern California, CA 90033, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Hung
authors.affiliation: WJWU & LYNN Institute for Stem Cell Research, 12145 Mora Drive, Santa Fe Springs, CA 90670, USA.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Chang
authors.affiliation: WJWU & LYNN Institute for Stem Cell Research, 12145 Mora Drive, Santa Fe Springs, CA 90670, USA.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Lin
authors.affiliation: Department of Cell & Neurobiology, Keck School of Medicine, University of Southern California, CA 90033, USA.
authors.forename: Shao-Yao
authors.initials: SY
authors.lastname: Ying
authors.affiliation: WJWU & LYNN Institute for Stem Cell Research, 12145 Mora Drive, Santa Fe Springs, CA 90670, USA shilungl@mirps.org.
authors.forename: Shi-Lung
authors.initials: SL
authors.lastname: Lin
mesh_terms: D001205:Ascorbic Acid / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000737:chemistry / Q000378:metabolism*; D005990:Glycerol / Q000737:chemistry / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057026:Induced Pluripotent Stem Cells / Q000737:chemistry / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012322:RNA Precursors; D034741:RNA, Small Interfering; D005990:Glycerol; D001205:Ascorbic Acid; D005998:Glycine