ABSTRACT
Skeletal myogenesis is orchestrated by distinct regulatory signaling pathways, including PI3K/AKT, that ultimately control muscle gene expression. Recently discovered myogenic micro-RNAs (miRNAs) are deeply implicated in muscle biology. Processing of miRNAs from their primary transcripts is emerging as a major step in the control of miRNA levels and might be well suited to be regulated by extracellular signals. Here we report that the RNA binding protein KSRP is required for the correct processing of primary myogenic miRNAs upon PI3K/AKT activation in myoblasts C2C12 and in the course of injury-induced muscle regeneration, as revealed by Ksrp knock-out mice analysis. PI3K/AKT activation regulates in opposite ways two distinct KSRP functions inhibiting its ability to promote decay of myogenin mRNA and activating its ability to favor maturation of myogenic miRNAs. This dynamic regulatory switch eventually contributes to the activation of the myogenic program.
Subject(s)
Muscle Development/physiology , Myoblasts, Skeletal/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA-Binding Proteins/metabolism , Trans-Activators/metabolism , Animals , Cell Line , Mice , Mice, Knockout , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle, Skeletal/injuries , Muscle, Skeletal/metabolism , Myogenin/genetics , Myogenin/metabolism , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , RNA Stability/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , Regeneration/physiology , Trans-Activators/geneticsABSTRACT
Electron diffraction in free-standing liquid-crystal films of N-(4-n-butoxybenzylidene)-4-n-octylaniline between 3 and 12 molecular layers thick reveals the unusual occurrence of the smectic-A' phase, a highly correlated isotropic liquid, on the surface of smectic-A films. The surface smectic-A-smectic-A' transition is found to be first order. Surprisingly, the temperature range of the subsequent surface hexatic-B phase is reduced with decreasing film thickness.
ABSTRACT
An unexpected three-stage melting transition has been observed in two-dimensional (2D) free-standing liquid-crystal films by in situ electron-diffraction and optical-reflectivity measurements. These data suggest the existence of two phases between the 2D solid and liquid: a hexatic phase and, at a higher temperature, an intermediate liquid phase with hexatic-like positional correlations ( approximately 40 angstroms) but no long-range orientational order. Previous high-resolution heat-capacity measurements have revealed a divergent-like anomaly at the hexatic-liquid transition that sharply contradicts the predictions of 2D melting theories. The observation of an intermediate isotropic phase may alter our understanding of 2D melting and lead to reconciliation between current experiments and theories.
