title: The protein kinase KIS impacts gene expression during development and fear conditioning in adult mice.
abstract: The brain-enriched protein kinase KIS (product of the gene UHMK1) has been shown to phosphorylate the human splicing factor SF1 in vitro. This phosphorylation in turn favors the formation of a U2AF(65)-SF1-RNA complex which occurs at the 3' end of introns at an early stage of spliceosome assembly. Here, we analyzed the effects of KIS knockout on mouse SF1 phosphorylation, physiology, adult behavior, and gene expression in the neonate brain. We found SF1 isoforms are differently expressed in KIS-ko mouse brains and fibroblasts. Re-expression of KIS in fibroblasts restores a wild type distribution of SF1 isoforms, confirming the link between KIS and SF1. Microarray analysis of transcripts in the neonate brain revealed a subtle down-regulation of brain specific genes including cys-loop ligand-gated ion channels and metabolic enzymes. Q-PCR analyses confirmed these defects and point to an increase of pre-mRNA over mRNA ratios, likely due to changes in splicing efficiency. While performing similarly in prepulse inhibition and most other behavioral tests, KIS-ko mice differ in spontaneous activity and contextual fear conditioning. This difference suggests that disregulation of gene expression due to KIS inactivation affects specific brain functions.
authors.affiliation: INSERM, UMR-S 839, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Manceau
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Nabel
authors.forename: Alexandre
authors.initials: A
authors.lastname: Maucuer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006948:Hyperkinesis / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C530659:Uhmk1 protein, mouse