Alternative polyadenylation of the amyloid protein precursor mRNA regulates translation.
The sequence of several cDNAs encoding the amyloid protein precursor showed that two polyadenylation sites of the mRNA are utilized; RNA blot analysis with different riboprobes indicated that this explains the difference between the two major 3.2 and 3.4 kb mRNAs found in the human brain. These two mRNAs, which contain the whole sequence of the natural molecules, were synthesized by in vitro transcription and translated in Xenopus oocytes. The long mRNA using the second polyadenylation site produced more protein than the short mRNA. The sequence contained within the two polyadenylation sites used in the 3' untranslated region of the amyloid protein precursor mRNA was also able to increase the production of the chicken lysozyme or the chloramphenicol acetyl transferase, as demonstrated by in vivo translation of different chimeric mRNAs obtained by in vitro transcription. This difference in protein production was also observed when chimeric cDNA constructs were transfected into Chinese hamster ovary cells. Since long mRNAs are not more stable than short mRNAs, the sequence contained within the two polyadenylation sites of the amyloid protein precursor mRNA increases the translation.
Laboratoire de Neurochimie, Université Catholique de Louvain, Bruxelles, Belgium.
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D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000502:physiology*; D002645:Chickens; D002678:Chimera; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D015342:DNA Probes; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D009113:Muramidase / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D010957:Plasmids; D011061:Poly A / Q000235:genetics*; D014176:Protein Biosynthesis; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014162:Transfection; D014981:Xenopus
D016564:Amyloid beta-Protein Precursor; D015342:DNA Probes; D012322:RNA Precursors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D011061:Poly A; D004247:DNA; D009113:Muramidase