An evolutionary conserved pattern of 18S rRNA sequence complementarity to mRNA 5′ UTRs and its implications for eukaryotic gene translation regulation

Abstract

There are several key mechanisms regulating eukaryotic gene expression at the level of protein synthesis. Interestingly, the least explored mechanisms of translational control are those that involve the translating ribosome per se, mediated for example via predicted interactions between the ribosomal RNAs (rRNAs) and mRNAs. Here, we took advantage of robustly growing large-scale data sets of mRNA sequences for numerous organisms, solved ribosomal structures and computational power to computationally explore the mRNA–rRNA complementarity that is statistically significant across the species. Our predictions reveal highly specific sequence complementarity of 18S rRNA sequences with mRNA 5′ untranslated regions (UTRs) forming a well-defined 3D pattern on the rRNA sequence of the 40S subunit. Broader evolutionary conservation of this pattern may imply that 5′ UTRs of eukaryotic mRNAs, which have already emerged from the mRNA-binding channel, may contact several complementary spots on 18S rRNA situated near the exit of the mRNA binding channel and on the middle-to-lower body of the solvent-exposed 40S ribosome including its left foot. We discuss physiological significance of this structurally conserved pattern and, in the context of previously published experimental results, propose that it modulates scanning of the 40S subunit through 5′ UTRs of mRNAs.

Deficiency of the adaptor protein SLy1 results in a natural killer cell ribosomopathy affecting tumor clearance

“…5E). Since the predominant material within the ribosome is rRNA (rRNA) and 18S rRNA is a critical component of the 40S subunit that facilitates binding to the 5′ untranslated region of mRNA, 29 we next verified the results of A254 absorbance by measuring 18S rRNA content by RT-PCR. Similar to A254 absorbance identical amount of 18S rRNA was evident in B6 wt and B6 SLy1− NK cells (Fig.…”

Translational dysregulation in cancer: eIF4A isoforms and sequence determinants of eIF4A dependence

“…A recent bioinformatic study demonstrated an evolutionary conserved pattern of complementarity between 18S rRNA and mRNA 5 -UTRs [59], providing weight to the argument that such interactions could be biologically significant. Furthermore, the rRNA regions showing significant complementarity to 5 -UTRs were found to be clustered within the evolutionarily recent expansion segments of 18S rRNA, which are exposed on the surface of the ribosome.…”

“…This would also provide a gratifying evolutionary hypothesis to explain the role of the expansion regions for translational regulation. Panek et al [59] hypothesize that interactions between mRNA exiting the scanning 40S ribosome form hybrid structures with complementary sequences in the 18S rRNA expansion regions and that these 'sticky elements' could impede scanning during translation initiation. eIF4A activity could therefore be required to unwind these duplexes during scanning and we feel this certainly deserves further investigation.…”

Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA

“…Conserved sequences indicate potential functions and/or play important roles in cell development and regulation [137][138][139]. As a rule, coding region sequences are highly conserved.…”