Endogenous polyamine function--the RNA perspective.

Helen L Lightfoot,Jonathan Hall

doi:10.1093/nar/gku837

Abstract

Recent progress with techniques for monitoring RNA structure in cells such as ‘DMS-Seq’ and ‘Structure-Seq’ suggests that a new era of RNA structure-function exploration is on the horizon. This will also include systematic investigation of the factors required for the structural integrity of RNA. In this context, much evidence accumulated over 50 years suggests that polyamines play important roles as modulators of RNA structure. Here, we summarize and discuss recent literature relating to the roles of these small endogenous molecules in RNA function. We have included studies directed at understanding the binding interactions of polyamines with polynucleotides, tRNA, rRNA, mRNA and ribozymes using chemical, biochemical and spectroscopic tools. In brief, polyamines bind RNA in a sequence-selective fashion and induce changes in RNA structure in context-dependent manners. In some cases the functional consequences of these interactions have been observed in cells. Most notably, polyamine-mediated effects on RNA are frequently distinct from those of divalent cations (i.e. Mg2+) confirming their roles as independent molecular entities which help drive RNA-mediated processes.

Highlights

Discovery and physical properties of polyaminesThe polyamine spermine (Figure 1) is a linear aliphatic nitrogenous base which was first isolated as the phosphate salt from human semen in 1678
As for metal ions [167], two distinct modes of binding to RNA can be expected for polyamines [105,111]: an orthodox non-specific manner, where polyamines diffuse within a restricted volume around the nucleic acid or its hydrated environment and a site-specific mode, where it is chelated in a defined binding pocket via direct interactions with distinct nucleic acid residues
These interactions will be governed by the polyamine structure, its protonation state, the RNA structure and sequence and the ionic environment

Summary

INTRODUCTION

The polyamine spermine (Figure 1) is a linear aliphatic nitrogenous base which was first isolated as the phosphate salt from human semen in 1678. These observations imply that the concentration of available cellular spermidine may be a decisive factor in the contribution of NS1 to inhibition of host translation by the virus [98] Taking these studies together, it can be concluded that spermidine (but not Mg2+) selectively stabilizes functionally relevant A-form RNA helices with bulged-out regions. The evidence suggests that this interaction, for at least some mRNAs, contributes to spermidine’s effect on translation In these examples the bulged helical regions were mainly U-rich stems in the initiation regions of mRNAs. The importance of a high U-content for spermidinemediated enhancement of polypeptide synthesis was previously noted in studies using E. coli and B. thuringiensis cell-free systems [100].

C Bulge Region

Findings

SUMMARY AND OUTLOOK