A possible novel interaction between the 3′‐end of 18 S ribosomal RNA and the 5'‐leader sequence of many eukaryotic messenger RNAs

Abstract

A novel interaction between the 5′‐untranslated region of eukaryotic messenger RNAs and non‐contiguous sequences in the 18 S ribosomal RNA is proposed. The small ribosomal RNA contains, at its 3′‐terminus, a heavily conserved hairpin structure. It is suggested that mRNA 5′‐leader sequence stabilises this structure by interacting with other conserved nucleotides which flank it. Sequences closely related to the required sequence (A—U—C—C—A—C—C) occur quite commonly in eukaryotic mRNAs and are often found immediately upstream from the AUG‐codon. This interaction may have a role in the events which lead up to the initiation of protein synthesis.

Comparative analysis of base correlations in 5′ untranslated regions of various species

“…Position − 3, widely thought to be the most important position in the Kozak sequence in regard to translational initiation, showed no remarkable base correlation with nearby bases, although I was high. Previous studies have suggested that 18S rRNA binds to the Kozak sequence (Hagenbuchle et al, 1978;Sargan et al, 1982;Sarge and Maxwell, 1991;Lagunez-Otero, 1993;Mauro and Edelman, 1997;Tranque et al, 1998;Verrier and Jean-Jean, 2000), but our results are inconsistent with this hypothesis. Stable binding would require sequential pairing between the 18S rRNA and Kozak sequence; however, our analyses failed to identify the expected conservation of and correlation between successive bases necessary for such binding to occur.…”

Comparison of the consensus sequence flanking translational start sites inDrosophilaand vertebrates

“…The taxonomic differences reported herein are also relevant to molecular models which propose that the mRNA translation start site is recognized by the 18S ribosomal RNA (2,3). A highly conserved stem-loop structure exists at the 3' end of the 18S RNA (10).…”

“…The importance of the other consensus nucleotides is more subtle and they exhibit an interaction effect with the state of the -3 position. Sargan and coworkers (3) have proposed that the recognition of the start site by the ribosome could be mediated through complementary pairing of the mRNA CCACC sequence between -5 and -1 (or at least a similar sequence nearby) and five nucleotides at the base of the highly conserved 18S rRNA stem loop structure. Thus this consensus sequence has considerable practical and theoretical value.…”

Evidence for Involvement of trans-Acting Factors in Selection of the AUG Start Codon during Eukaryotic Translational Initiation

“…In the absence of a Ϫ3 purine, the presence of a guanosine at position ϩ4 is essential for efficient AUG usage (25). Although interactions between the 5Ј-CC(A/G)CCAUGG-3Ј sequences in the mRNA and specific regions located in 18S rRNA have been postulated (25,37), experimental evidence for this interaction has not been provided. Thus, the mechanism of recognition of the start site AUG codon, surrounded by particular bases, is not clear.…”