AUUUA sequences compromise human insulin-like growth factor binding protein-1 mRNA stability

Authors
Citation
E. Gay et S. Babajko, AUUUA sequences compromise human insulin-like growth factor binding protein-1 mRNA stability, BIOC BIOP R, 267(2), 2000, pp. 509-515
Citations number
38
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006291X → ACNP
Volume
267
Issue
2
Year of publication
2000
Pages
509 - 515
Database
ISI
SICI code
0006-291X(20000119)267:2<509:ASCHIG>2.0.ZU;2-H
Abstract
The instability of IGFBP-1 mRNA appears to play a role in regulating the ex pression of the IGFBP-1 gene, the 3' region of which contains five ATTTA se quences. We have studied the implication of these sequences for IGFBP-1 mRN A destabilization. Six plasmids were constructed, containing increasingly s horter lengths of IGFBP-1 cDNA, each with a successive ATTTA sequence delet ed from the 3' end. These were stably transfected into two non-IGFBP-1-expr essing (cervical carcinoma and neuroblastoma) cell lines. Kinetics studies following inhibition of transcription showed that (I) the half-life of the full-length messenger was 2.80 +/- 0.32 h; (2) deletion of each successive sequence (particularly the second and the fourth) yielded a transcript of i ncreasing stability; and (3) the half-life of the AUUUA-free mRNA was 26.65 +/- 1.65 h. Although the primary source of IGFBP-1 is the liver, our resul ts demonstrate that destabilization of its mRNA is not liver-specific. The ATTTA consensus sequences in the 3' untranslated region of the IGFBP-1 gene therefore provide a posttranscriptional regulation pathway that, combined with transcriptional regulation, may account for the variations in IGFBP-1 expression with developmental stage, nutritional status, and hormonal envir onment. (C) 2000 Academic Press.