Regulation of gene expression by alternative polyadenylation and mRNA instability in hyperglycaemic mesangial cells.
We have used mRNA differential display to identify a novel high-glucose-regulated gene (HGRG-14) in human mesangial cells cultured for up to 21 days in 30 mM d-glucose. The mRNA of HGRG-14 seems to be regulated post-transcriptionally and encodes a small polypeptide of molecular mass 13 kDa. The native protein occurs as a dimer. The recombinant protein is a substrate for casein kinase II kinase. At high glucose concentrations, HGRG-14 protein levels decrease. This correlates with the appearance of a long form of HGRG-14 mRNA under high-glucose conditions. This form has a long 3' untranslated region containing several ATTTA RNA-destabilizing sequences and has a short half-life. A truncated, more stable mRNA that lacks the long 3' untranslated region is produced at 4 mM d-glucose. The switch from the truncated to the long-form transcript is detected within 2 h of exposure to 30 mM d-glucose, indicating that hyperglycaemic conditions have an acute effect on HGRG-14 mRNA processing.
Abdel Wahab
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N
Molecular Pathology Section, Division of Biomedical Sciences, Imperial College School of Medicine, BMS Building, South Kensington, London SW7 2AZ, U.K.
Gibbs
J
J
Mason
R M
RM
D020413:3' Untranslated Regions; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D047390:Casein Kinase II; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003429:Cross Reactions; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D010750:Phosphoproteins; D010766:Phosphorylation; D011061:Poly A; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D020413:3' Untranslated Regions; D002352:Carrier Proteins; C116653:HGRG-14 protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D003609:Dactinomycin; D011061:Poly A; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases