Expression of mouse igf2 mRNA-binding protein 3 and its implications for the developing central nervous system.
Functional analyses of neural RNA-binding proteins have focused mainly on their roles as modulators of posttranscriptional gene regulation, e.g., alternative splicing, dendritic mRNA localization, and local translation. Here we identified a mouse homologue of human IMP3, which is known to bind to and repress the translation of igf2 leader 3 mRNA. The mouse igf2 mRNA-binding protein 3 (mIMP3) is a member of the zipcode binding protein-1 (ZBP-1) family previously reported in chick fibroblast cells. mIMP3 was expressed in undifferentiated neuroepithelial cells and some postmitotic neurons at early embryonic stages (E10.5--E12.5), and its expression level decreased after the midembryonic stage (E12.5) until birth. The expression profile of mIMP3 is very similar to that of mouse igf2 leader 3 mRNA. In vitro UV cross-linking experiments showed that mIMP3 preferentially bound to igf2 leader 3 mRNA rather than igf2 leader 4 mRNA and did not bind the zipcode region of beta-actin or c-myc mRNA. Furthermore, persistent expression of mIMP3 protein in an undifferentiated P19 cell line revealed that mIMP3 inhibited neuronal differentiation morphologically and immunohistochemically. Taken together, these observations raise the possibility that mIMP3 represses neuronal differentiation through the regulation of igf2 mRNA expression.
Mori
H
H
Division of Neuroanatomy, Department of Neuroscience, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Sakakibara
S
S
Imai
T
T
Nakamura
Y
Y
Iijima
T
T
Suzuki
A
A
Yuasa
Y
Y
Takeda
M
M
Okano
H
H
D020121:5' Untranslated Regions / Q000378:metabolism / Q000528:radiation effects; D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology* / Q000254:growth & development; D002454:Cell Differentiation / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D005810:Multigene Family; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000528:radiation effects; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D020121:5' Untranslated Regions; D030161:Avian Proteins; C406144:IGF2BP1 protein, human; C498780:IGF2BP3 protein, human; C498777:Igf2bp3 protein, mouse; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C498636:ZBP1 protein, Gallus gallus; D007335:Insulin-Like Growth Factor II