Mammalian homologs of Drosophila ELAV localized to a neuronal subset can bind in vitro to the 3' UTR of mRNA encoding the Id transcriptional repressor.
Mammalian cDNAs encoding a rat (Rel-N1) and a human (Hel-N1) neuronal RNA-binding protein have been cloned and characterized with respect to tissue specificity, neuroanatomical localization, and RNA binding specificity. Both proteins are highly similar to the product of the Drosophila elav gene, which is expressed in all neurons of the fly and is required for development of the nervous system. However, in situ hybridization of rat tissues demonstrated more restricted expression of Rel-N1 mRNA within a subset of neurons of the hippocampus, cortex, and other regions of the gray matter, but not in glial cells or white matter. In vitro RNA binding experiments demonstrated that Hel-N1 can bind to the 3' untranslated region (3' UTR) of Id mRNA, a transcript that encodes a helix-loop-helix transcriptional repressor that is abundantly expressed in undifferentiated neural precursors. Sequences characterized for Hel-N1 binding were also abundantly present in the 3' UTR of the Drosophila extramacrochaetae mRNA, which encodes an Id homolog. Thus, we have identified a potential link between a neuronal 3' UTR RNA-binding protein and regulatory transcription factors involved in neural development. These findings are interpreted in light of recent studies in which mRNA 3' UTRs were found to be important for the regulation of cell growth and differentiation.
King
P H
PH
Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710.
Levine
T D
TD
Fremeau
R T
RT
Keene
J D
JD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004330:Drosophila / Q000235:genetics*; D051959:ELAV Proteins; D000067777:ELAV-Like Protein 2; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D012097:Repressor Proteins; D015183:Restriction Mapping; D012261:Ribonucleoproteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051959:ELAV Proteins; D000067777:ELAV-Like Protein 2; C086811:ELAVL2 protein, human; C490170:Elavl2 protein, rat; C497453:ID1 protein, human; C497454:ID1 protein, rat; D051798:Inhibitor of Differentiation Protein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors