Control of insulin mRNA stability in rat pancreatic islets. Regulatory role of a 3'-untranslated region pyrimidine-rich sequence.
Stabilization of insulin mRNA in response to glucose is a significant component of insulin production, but the mechanisms governing this process are unknown. We presently observe that insulin mRNA is a highly abundant messenger and that the content of this mRNA is mainly controlled by changes in messenger stability. We also demonstrate specific binding of the polypyrimidine tract-binding protein to a pyrimidine-rich sequence located in the 3'-untranslated region (3'-UTR) of insulin mRNA. This binding was increased in vitro by dithiothreitol and in vivo by glucose. Inhibition of polypyrimidine tract-binding protein binding to the pyrimidine-rich sequence by mutation of the core binding site resulted in a destabilization of a reporter gene mRNA. Thus, glucose-induced binding of polypyrimidine tract-binding protein to the 3'-UTR of insulin mRNA could be a necessary event in the control of insulin mRNA levels.
Tillmar
Linda
L
Department of Medical Cell Biology, Uppsala University, Uppsala S-751 23, Sweden.
Carlsson
Carina
C
Welsh
Nils
N
D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D002458:Cell Fractionation; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000502:physiology; D038941:Polypyrimidine Tract-Binding Protein; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D014020:Tissue Extracts / Q000737:chemistry
D020413:3' Untranslated Regions; D007328:Insulin; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D014020:Tissue Extracts; D038941:Polypyrimidine Tract-Binding Protein; D005947:Glucose; D004229:Dithiothreitol