title: Gld2-catalyzed 3' monoadenylation of miRNAs in the hippocampus has no detectable effect on their stability or on animal behavior.
abstract: Gld2, a noncanonical cytoplasmic poly(A) polymerase, interacts with the RNA binding protein CPEB1 to mediate polyadenylation-induced translation in dendrites of cultured hippocampal neurons. Depletion of Gld2 from the hippocampus leads to a deficit in long-term potentiation evoked by theta burst stimulation. At least in mouse liver and human primary fibroblasts, Gld2 also 3' monoadenylates and thereby stabilizes specific miRNAs, which enhance mRNA translational silencing and eventual destruction. These results suggest that Gld2 would be likely to monoadenylate and stabilize miRNAs in the hippocampus, which would produce measurable changes in animal behavior. We now report that using Gld2 knockout mice, there are detectable alterations in specific miRNA monoadenylation in the hippocampus when compared to wild type, but that these modifications produce no detectable effect on miRNA stability. Moreover, we surprisingly find no overt change in animal behavior when comparing Gld2 knockout to wild-type mice. These data indicate that miRNA monoadenylation-mediated stability is cell type-specific and that monoadenylation has no measurable effect on higher cognitive function.
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Fernanda
authors: F
authors: Mansur
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Maria
authors: M
authors: Ivshina
authors: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, California 92521, USA.
authors: Weifeng
authors: W
authors: Gu
authors: Animal Research and Development, Mousera, San Mateo, California 94402, USA.
authors: Laura
authors: L
authors: Schaevitz
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Emily
authors: E
authors: Stackpole
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Sharvari
authors: S
authors: Gujja
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Yvonne J K
authors: YJ
authors: Edwards
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Joel D
authors: JD
authors: Richter
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011062:Polynucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism*; D026721:RNA 3' End Processing; D020871:RNA Stability
chemical_list: D035683:MicroRNAs; C575491:Gld2 protein, mouse; D011062:Polynucleotide Adenylyltransferase
keywords: Gld2; behavior; hippocampus; miRNA; monoadenylation