Mapping and characterization of the minimal internal ribosome entry segment in the human c-myc mRNA 5′ untranslated region

The human c -myc proto-oncogene is transcribed from four alternative promoters generating transcripts with 5′ untranslated regions of various lengths. These transcripts encode two proteins, c-Myc1 and c-Myc2, from two initiation codons, CUG and AUG, respectively. We and others have previously demons...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Oncogene 2004-01, Vol.23 (1), p.267-277
Hauptverfasser: Cencig, Sabrina, Nanbru, Cécile, Le, Shu-Yun, Gueydan, Cyril, Huez, Georges, Kruys, Véronique
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The human c -myc proto-oncogene is transcribed from four alternative promoters generating transcripts with 5′ untranslated regions of various lengths. These transcripts encode two proteins, c-Myc1 and c-Myc2, from two initiation codons, CUG and AUG, respectively. We and others have previously demonstrated that the region of c- myc transcripts between nucleotides (nt) –363 and –94 upstream from the CUG start codon contained an internal ribosome entry site leading to the cap-independent translation of c- myc open reading frames (ORFs). Here, we mapped a 50-nt sequence (−143 −94), which is sufficient to promote internal translation initiation of c- myc ORFs. Interestingly, this 50-nt element can be further dissected into two segments of 14 nt, each capable of activating internal translation initiation. We also demonstrate that this 50-nt element acts as the ribosome landing site from which the preinitiation ribosomal complex scans the mRNA until the CUG or AUG start codons.
ISSN:0950-9232
1476-5594
DOI:10.1038/sj.onc.1207017