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Molecular Mechanism of the cSHMT Internal Ribosome Entry Site (IRES)
Author(s) -
Fox Jennifer Theresa,
Woeller Collynn F,
Stover Patrick J
Publication year - 2006
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.20.5.a1372-c
The 5′ untranslated region (UTR) of the cytoplasmic serine hydroxymethyltransferase (cSHMT) transcript contains a novel heavy chain ferritin (HCF)‐responsive internal ribosome entry site (IRES) that regulates folate‐mediated one‐carbon metabolism. In this study, the mechanism of cSHMT IRES activation was investigated. IRES activity was shown to be stimulated by the cSHMT 3′ UTR, which contains a CUGBP1 binding site. CUGBP1 is shown to physically interact with HCF, indicating that CUGBP1 and HCF act together to activate IRES activity. Both CUGBP1 and a 14 kDa HCF fragment are shown to bind the cSHMT 5′ and 3′ UTRs. Collectively, these data indicate that the cSHMT 5′ and 3′ UTR function in concert to activate IRES mediated translation. Furthermore, mutational analysis of the cSHMT 5′ UTR indicates that ribosome scanning is not involved in IRES activation and implicates two nucleotides as being essential for IRES function. (supported by DK58144)