L-Myc protein synthesis is initiated by internal ribosome entry

RNA. 2004 Feb;10(2):287-98. doi: 10.1261/rna.5138804.

Abstract

An internal ribosome entry segment (IRES) has been identified in the 5' untranslated region (5' UTR) of two members of the myc family of proto-oncogenes, c-myc and N-myc. Hence, the synthesis of c-Myc and N-Myc polypeptides can involve the alternative mechanism of internal initiation. Here, we show that the 5' UTR of L-myc, another myc family member, also contains an IRES. Previous studies have shown that the translation of mRNAs containing the c-myc and N-myc IRESs can involve both cap-dependent initiation and internal initiation. In contrast, the data presented here suggest that internal initiation can account for all of the translation initiation that occurs on an mRNA with the L-myc IRES in its 5' UTR. Like many other cellular IRESs, the L-myc IRES appears to be modular in nature and the entire 5' UTR is required for maximum IRES efficiency. The ribosome entry window within the L-myc IRES is located some distance upstream of the initiation codon, and thus, this IRES uses a "land and scan" mechanism to initiate translation. Finally, we have derived a secondary structural model for the IRES. The model confirms that the L-myc IRES is highly structured and predicts that a pseudoknot may form near the 5' end of the mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / metabolism
  • Animals
  • Base Sequence
  • Binding Sites
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / metabolism*
  • Ribosomes / metabolism*

Substances

  • 5' Untranslated Regions
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger