Visinin-like protein (VILIP) is a neuron-specific calcium-dependent double-stranded RNA-binding protein.
Double-stranded RNA-binding proteins function in regulating the stability, translation, and localization of specific mRNAs. In this study, we have demonstrated that the neuron-specific, calcium-binding protein, visinin-like protein (VILIP) contains one double-stranded RNA-binding domain, a protein motif conserved among many double-stranded RNA-binding proteins. We showed that VILIP can specifically bind double-stranded RNA, and this interaction specifically requires the presence of calcium. Mobility shift studies indicated that VILIP binds double-stranded RNA as a single protein-RNA complex with an apparent equilibrium dissociation constant of 9.0 x 10(-6) M. To our knowledge, VILIP is the first double-stranded RNA-binding protein shown to be calcium-dependent. Furthermore, VILIP specifically binds the 3'-untranslated region of the neurotrophin receptor, trkB, an mRNA localized to hippocampal dendrites in an activity-dependent manner. Given that VILIP is also expressed in the hippocampus, these data suggest that VILIP may employ a novel, calcium-dependent mechanism to regulate its binding to important localized mRNAs in the central nervous system.
Mathisen
P M
PM
Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. mathisp@ccf.org
Johnson
J M
JM
Kawczak
J A
JA
Tuohy
V K
VK
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051596:Neurocalcin; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020813:Receptor, trkB / Q000235:genetics; D044169:Receptors, Calcium-Sensing; D017386:Sequence Homology, Amino Acid
D020413:3' Untranslated Regions; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D051596:Neurocalcin; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D044169:Receptors, Calcium-Sensing; C496689:Vsnl1 protein, mouse; D020813:Receptor, trkB; D002118:Calcium