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Control of human achaete‐scute homologue‐1 (hASH1) mRNA translation by fragile X‐mental retardation protein (FMRP)
Author(s) -
Fähling Michael,
Mrowka Ralf,
Steege Andreas,
Kirschner Karin Michaela,
Benko Edgar,
Persson Pontus Börje,
Thiele Bernd Joachim,
Scholz Holger
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.607.7
Subject(s) - messenger rna , biology , polysome , untranslated region , microbiology and biotechnology , translation (biology) , reporter gene , fragile x syndrome , translational regulation , protein biosynthesis , gene expression , gene , ribosome , rna , genetics
The basic helix‐loop‐helix transcription factor human achaete‐scute homologue‐1 (hASH1; ASCL1) is required for normal development of the nervous system and has been implicated in the formation of neuroendocrine tumors. Here we show that the mRNA of hASH1 is a new target of the fragile X‐mental retardation protein (FMRP). We provide several lines of evidence that hASH1 and FMRP are co‐expressed in distinct areas of the nervous system, e.g. by double‐immunofluorescent staining of both proteins in newborn mice brain. Forced expression of FMRP significantly increased hASH1 protein, but not its mRNA, in cultured HEK293 cells. Sucrose density gradient centrifugation revealed that hASH1 transcripts were translocated into a translationally active polysomal fraction in response to increased FMRP level. Luciferase reporter gene assays indicated that the influence of FMRP is mediated by interaction with the 5′‐untranslated region (UTR) of hASH1 mRNA. The responsible cis‐element was mapped by UV‐cross‐linking experiments and reporter mutagenesis assays to a (U)10‐sequence. In conclusion, hASH1 is a novel downstream target of FMRP. Improved translation efficiency of hASH1 mRNA by FMRP may represent an important switch in neuronal differentiation.