An alternatively-spliced exon in the 5'-UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem-mediated decay.
Haem controls its own synthesis in non-erythroid cells primarily by regulation of ALAS1 mRNA stability. Alternative splicing of human ALAS1 generates two mRNAs with different 5'-UTRs: a major one, where exon 1B is omitted, and a minor form containing exon 1B. We show that, unlike the major ALAS1 mRNA, the minor form was resistant to haem-mediated decay. Furthermore, we demonstrate that the ALAS1 5'-UTR alone did not confer haem-mediated decay upon a heterologous mRNA and the inclusion of exon 1B inhibited translation. These data suggest that translation of ALAS1 mRNA itself might be required for destabilisation in response to haem.
Roberts
Andrew G
AG
Department of Medical Biochemistry and Immunology, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK.
Redding
Sadie J
SJ
Llewellyn
David H
DH
D020121:5' Untranslated Regions / Q000235:genetics*; D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics*; D045744:Cell Line, Tumor; D003609:Dactinomycin / Q000494:pharmacology; D005091:Exons / Q000235:genetics*; D006418:Heme / Q000494:pharmacology*; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects*; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D003609:Dactinomycin; D006418:Heme; D000624:5-Aminolevulinate Synthetase