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An alternatively‐spliced exon in the 5′‐UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem‐mediated decay
Author(s) -
Roberts Andrew G.,
Redding Sadie J.,
Llewellyn David H.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.12.080
Subject(s) - messenger rna , translation (biology) , exon , five prime untranslated region , untranslated region , microbiology and biotechnology , chemistry , three prime untranslated region , rna splicing , biophysics , biology , physics , rna , biochemistry , gene
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.