Functional importance of RNA interactions in selection of translation initiation codons

Abstract

SummaryRNA base pairing between the initiation codon and anticodon loop of initiator tRNA is essential but not sufficient for the selection of the 'correct' mRNA translational start site by ribosomes. In prokaryotes, additional RNA interactions between small ribosomal subunit RNA and mRNA sequences just upstream of the start codon can efficiently direct the ribosome to the initiation site. Although there is presently no proof for a similar important ribosomal RNA interaction in eukaryotes, the 5Ј non-coding regions of their mRNAs and 'consensus sequences' surrounding initiation codons have been shown to be strong determinants for initiation-site selection, but the exact mechanisms are not yet understood. Intramolecular base pairing in mRNA and participation of translation initiation factors can strongly influence the formation of mRNA-small ribosomal subunit-initiator tRNA complexes and modulate translational activities in both prokaryotes and eukaryotes. Only recently has it been appreciated that alternative mechanisms may also contribute to the selection of initiation codons in all organisms. Although direct proof is currently lacking, there is accumulating evidence that additional cis-acting mRNA elements and trans-acting proteins may form specific 'bridging' interactions with ribosomes during translation initiation.

Deletion analysis of cspA of Escherichia coli: requirement of the AT‐rich UP element for cspA transcription and the downstream box in the coding region for its cold shock induction

“…8C and Table 1. This result agrees with the proposal by Sprengart et al (1990;; for a review, see also Sprengart and Porter, 1997) that the sequence downstream of the initiation codon, called the downstream box (DB), interacts with the complementary sequence near the decoding region of 16S rRNA, called the anti-downstream box (ADB), to mediate efficient translation from the initiation codon even in the absence of the Shine-Dalgarno sequence (Sprengart et al, 1996;Wu and Janssen, 1996).…”

“…This feature of DBs in the cold shock genes with an extra sequence between the initiation codon and DB may be important for the most effective formation of translation initiation complexes. Consistent with this notion is that the DB of the highly active T7 gene 10 is also located 9 bases downstream of the initiation codon (Sprengart et al 1996; for a review, see Sprengart and Porter, 1997). The genes for other cold shock proteins contain DBs starting from the initiation codon (Table 1).…”

“…This result led us to find that the translational efficiency of the cspA mRNA plays the major role in the production of CspA during acclimation phase. The cspA mRNA contains a complementary sequence near the decoding region of 16S rRNA, and this complementary sequence is located 12 bases downstream of the initiation codon, thus designated the downstream box (DB) (for review, see Sprengart and Porter, 1997). The DB is known to enhance translation initiation even in the absence of the Shine-Dalgarno sequence (Sprengart et al, 1996;Wu and Janssen, 1996).…”

Identification of Novel and Widely Expressed Cancer/Testis Gene Isoforms That Elicit Spontaneous Cytotoxic T-Lymphocyte Reactivity to Melanoma

“…The TAG genes appear to be authentic in that they are capped at the 5Ј end, have an initiation codon (albeit nonstandard), exon/intron splicing, a stop codon, and a polyA tail. Initiation codons other than AUG have previously been described in eukaryotes (25), and two such codons (CUG is present twice, ACG is present once) are located upstream and in-frame with the sequence coding for the RLSNRLLLR peptide. Like the AUG initiation codon, nonstandard initiation codons are almost always found in concert with purines (A or G) at position Ϫ3 and/or ϩ4 relative to the initiation site (25).…”

Discrimination of 5′‐terminal start codons by translation initiation factor 3 is mediated by ribosomal protein S1

“…The e¡ect of the rpsB mutation was attributed to an increased accessibility of the anti-downstream box, which has been suggested to be located in the penultimate stem of 16S rRNA [3,4], for the downstream box positioned in the immediate vicinity of the start codon of cI mRNA [2]. However, the existence of this interaction has been questioned recently [5].…”