Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming
نویسندگان
چکیده
Noncoding microRNAs inhibit translation and lower the transcript stability of coding mRNA, however miR-369 s, in aberrant silencing genomic regions, stabilizes target proteins under cellular stress. We found that in vitro differentiation of embryonic stem cells led to chromatin methylation of histone H3K4 at the miR-369 region on chromosome 12qF in mice, which is expressed in embryonic cells and is critical for pluripotency. Proteomic analyses revealed that miR-369 stabilized translation of pyruvate kinase (Pkm2) splicing factors such as HNRNPA2B1. Overexpression of miR-369 stimulated Pkm2 splicing and enhanced induction of cellular reprogramming by induced pluripotent stem cell factors, whereas miR-369 knockdown resulted in suppression. Furthermore, immunoprecipitation analysis showed that the Argonaute complex contained the fragile X mental retardation-related protein 1 and HNRNPA2B1 in a miR-369-depedent manner. Our findings demonstrate a unique role of the embryonic miR-369-HNRNPA2B1 axis in controlling metabolic enzyme function, and suggest a novel pathway linking epigenetic, transcriptional, and metabolic control in cell reprogramming.
منابع مشابه
O-GlcNAcylation and Metabolic Reprograming in Cancer
Although cancer metabolism has received considerable attention over the past decade, our knowledge on its specifics is still fragmentary. Altered cellular metabolism is one of the most important hallmarks of cancer. Cancer cells exhibit aberrant glucose metabolism characterized by aerobic glycolysis, a phenomenon known as Warburg effect. Accelerated glucose uptake and glycolysis are main charac...
متن کاملExpression Analysis of Cellular Mir-29a and mir-29b in HIV Positive Patients
Abstract Background and Objective: Various cellular factors affect the process of HIV activity. One of these cellular factors are structures known as microRN that are expected to be involved in controlling HIV replication and infectivity. The expression of one or a set of them may represent the patient's clinical conditions. In this study, ...
متن کاملNoncanonical function of DGCR8 controls mESC exit from pluripotency
Mouse embryonic stem cells (mESCs) deficient for DGCR8, a key component of the microprocessor complex, present strong differentiation defects. However, the exact reasons impairing their commitment remain elusive. The analysis of newly generated mutant mESCs revealed that DGCR8 is essential for the exit from the pluripotency state. To dissociate canonical versus noncanonical functions of DGCR8, ...
متن کاملAWARD NUMBER: W81XWH-13-1-0354 TITLE: “Targeting the Adipocyte-Tumor Cell Interaction in Prostate Cancer Treatment” PRINCIPAL INVESTIGATOR:
s and presentations: “Nutrient sensing and Cancer Metabolism by the p62 autophagy pathway” University of Pennsylvania, Philadelphia, 2014. Speaker (Moscat). “New role of metabolic reprograming in stroma-induced tumorigenesis” Centre for Genome Regulation, Barcelona, Spain, 2014. Speaker (Moscat). “Metabolic Reprogramming by the p62 Pathway in Cancer” in the “2014 ASIP Annual Meeting at Experime...
متن کاملMolecular Imaging of Metabolic Reprograming in Mutant IDH Cells
Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) have recently been identified as drivers in the development of several tumor types. Most notably, cytosolic IDH1 is mutated in 70-90% of low-grade gliomas and upgraded glioblastomas, and mitochondrial IDH2 is mutated in ~20% of acute myeloid leukemia cases. Wild-type IDH catalyzes the interconversion of isocitrate to α-ketoglutara...
متن کامل