Protein Synthesis in Eukaryotes: The Growing Biological Relevance of Cap-Independent Translation Initiation

Biol Res. 2005;38(2-3):121-46. doi: 10.4067/s0716-97602005000200003.


Ribosome recruitment to eukaryotic mRNAs is generally thought to occur by a scanning mechanism, whereby the 40S ribosomal subunit binds in the vicinity of the 5'cap structure of the mRNA and scans until an AUG codon is encountered in an appropriate sequence context. Study of the picornaviruses allowed the characterization of an alternative mechanism of translation initiation. Picornaviruses can initiate translation via an internal ribosome entry segment (IRES), an RNA structure that directly recruits the 40S ribosomal subunits in a cap and 5' end independent fashion. Since its discovery, the notion of IRESs has extended to a number of different virus families and cellular RNAs. This review summarizes features of both cap-dependent and IRES-dependent mechanisms of translation initiation and discusses the role of cis-acting elements, which include the 5' cap, the 5'-untranslated region (UTR) and the poly(A) tail as well as the possible roles of IRESs as part of a cellular stress response mechanism and in the virus replication cycle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 5' Untranslated Regions / genetics
  • 5' Untranslated Regions / metabolism*
  • Animals
  • Cells, Cultured
  • Eukaryotic Cells / metabolism*
  • Picornaviridae / genetics
  • Picornaviridae / metabolism*
  • Poly(A)-Binding Proteins / metabolism
  • Protein Biosynthesis / genetics*
  • RNA Cap-Binding Proteins / metabolism
  • RNA Caps / genetics
  • RNA Caps / metabolism*
  • RNA, Messenger
  • Virus Replication


  • 5' Untranslated Regions
  • Poly(A)-Binding Proteins
  • RNA Cap-Binding Proteins
  • RNA Caps
  • RNA, Messenger