Developmentally regulated instability of the GPI-PLC mRNA is dependent on a short-lived protein factor.
The expression of the vast majority of protein coding genes in trypanosomes is regulated exclusively at the post-transcriptional level. Developmentally regulated mRNAs that vary in levels of expression have provided an insight into one mechanism of regulation; a decrease in abundance is due to a shortened mRNA half-life. The decrease in half-life involves cis-acting elements in the 3' untranslated region of the mRNA. The trans-acting factors necessary for the increased rate of degradation remain uncharacterized. The GPI-PLC gene in Trypanosoma brucei encodes a phospholipase C expressed in mammalian bloodstream form, but not in the insect procyclic form. Here, it is reported that the differential expression of the GPI-PLC mRNA also results from a 10-fold difference in half-life. Second, the instability of the GPI-PLC mRNA in procyclic forms can be reversed by the inhibition of protein synthesis. Third, specifically blocking the translation of the GPI-PLC mRNA in procyclic forms by the inclusion of a hairpin in the 5' untranslated region does not result in stabilization of the mRNA. Thus, the effect of protein synthesis inhibitors in stabilizing the GPI-PLC mRNA operates in trans through a short-lived factor dependent on protein synthesis.
Webb
Helena
H
Department of Biochemistry 80 Tennis Court Road, Cambridge CB2 1GA, UK.
Burns
Roisin
R
Ellis
Louise
L
Kimblin
Nicola
N
Carrington
Mark
M
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D054800:Glycosylphosphatidylinositol Diacylglycerol-Lyase; D006207:Half-Life; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000235:genetics* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000502:physiology*; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D016053:RNA, Protozoan / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development*
D011500:Protein Synthesis Inhibitors; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054800:Glycosylphosphatidylinositol Diacylglycerol-Lyase