title: 14-3-3 protein binds to the low molecular weight neurofilament (NFL) mRNA 3' UTR.
abstract: We have previously reported that altered stability of low molecular weight neurofilament (NFL) mRNA in lumbar spinal cord homogenates in amyotrophic lateral sclerosis (ALS) is associated with altered expression of trans-acting 3' UTR mRNA binding proteins. We have identified two hexanucleotide motifs as the main cis elements and, using LC/MS/MS of peptide digests of NFL 3' UTR interacting proteins from human spinal cord, observed that 14-3-3 proteins interact with these motifs. 14-3-3 beta, zeta, tau, gamma, and eta isoforms were found to be expressed in human spinal cord. Each isoform was expressed in vitro and shown to interact with NFL 3' UTR mRNA. Mutation of one or both motifs resulted in decreased 14-3-3 interaction, changes in predicted mRNA structure or alteration in stability of the mRNA. These data show a novel interaction for 14-3-3 with NFL mRNA, and suggests that 14-3-3 may play a role in regulating NFL mRNA stability.
authors.affiliation: Cell Biology Research Group, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada N6A 5K8.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Ge
authors.forename: Kathryn
authors.initials: K
authors.lastname: Volkening
authors.forename: Cheryl
authors.initials: C
authors.lastname: Leystra-Lantz
authors.forename: Howard
authors.initials: H
authors.lastname: Jaffe
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Strong
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D020413:3' Untranslated Regions; D016900:Neurofilament Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C044882:neurofilament protein L