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PMID: 9092640 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of two proteins that bind to a pyrimidine-rich sequence in the 3'-untranslated region of GAP-43 mRNA.

Nucleic acids research ·Vol. 25 ·No. 6 ·1997-03-15 ·Pages 1281-8

Irwin N, Baekelandt V, Goritchenko L, Benowitz LI

Abstract

GAP-43 is a membrane phosphoprotein that is important for the development and plasticity of neural connections. In undifferentiated PC12 pheochromocytoma cells, GAP-43 mRNA degrades rapidly ( t = 5 h), but becomes stable when cells are treated with nerve growth factor. To identify trans- acting factors that may influence mRNA stability, we combined column chromatography and gel mobility shift assays to isolate GAP-43 mRNA binding proteins from neonatal bovine brain tissue. This resulted in the isolation of two proteins that bind specifically and competitively to a pyrimidine-rich sequence in the 3'-untranslated region of GAP-43 mRNA. Partial amino acid sequencing revealed that one of the RNA binding proteins coincides with FBP (far upstream element binding protein), previously characterized as a protein that resembles hnRNP K and which binds to a single-stranded, pyrimidine-rich DNA sequence upstream of the c -myc gene to activate its expression. The other binding protein shares sequence homology with PTB, a polypyrimidine tract binding protein implicated in RNA splicing and regulation of translation initiation. The two proteins bind to a 26 nt pyrimidine-rich sequence lying 300 nt downstream of the end of the coding region, in an area shown by others to confer instability on a reporter mRNA in transient transfection assays. We therefore propose that FBP and the PTB-like protein may compete for binding at the same site to influence the stability of GAP-43 mRNA.

MeSH Terms
Adrenal Gland Neoplasms Amino Acid Sequence Animals Animals, Newborn Base Sequence Binding Sites Brain/metabolism Cattle Computer Simulation GAP-43 Protein Genes, myc Humans Membrane Glycoproteins/biosynthesis Mice Models, Structural Molecular Sequence Data Nerve Tissue Proteins/biosynthesis PC12 Cells Peptide Fragments/chemistry,isolation & purification Pheochromocytoma Phosphoproteins/biosynthesis RNA, Messenger/chemistry,metabolism RNA-Binding Proteins/chemistry,isolation & purification,metabolism Rats Sequence Homology, Nucleic Acid
Chemicals
GAP-43 Protein Membrane Glycoproteins Nerve Tissue Proteins Peptide Fragments Phosphoproteins RNA, Messenger RNA-Binding Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Irwin N
Department of Neurosurgery, Children's Hospital, Boston, MA 02115, USA. irwin_c@a1.tch.harvard.edu
Baekelandt V
Goritchenko L
Benowitz L I
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/25.6.1281
Email
irwin_c@a1.tch.harvard.edu
Published
1997-03-15
Pages
1281-8
Language
English
Region
England
NLM ID
0411011
PMCID
PMC146556
Subset
IM
Grants
NEI NIH HHS · EY 05690 · United States
External Links
PubMed source DOI: 10.1093/nar/25.6.1281 PMC Full Text View journal details
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