Endogenous polyamine function--the RNA perspective

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.

Figure 1.

Chemical structures of the polyamines and polyamine analogues discussed throughout this review.

Figure 2.

(A) Predicted structures of the initiation regions of OppA, RMF, RpoE and CpxR (only relevant sections shown). The nucleotide residues of the SD sequences are boxed and those of the initiation codon (AUG) circled. Stem I of OppA is boxed. (B) Mutants of the bulged stems used in the overexpression or biophysical studies. Highlighted: green—nucleotide (nt) deletion; blue—nt addition; red—nt mutated; purple—nt conformational changes.

Figure 3.

Summary of ABA-spermine cross-linking sites in 16S rRNA of E. coli. The arrows, discontinuous or solid, indicate sites labeling by 50 or 300 μM ABA-spermine, respectively. Long arrows—strong cross-links; medium arrows—intermediate cross-links; short arrows—weak cross-links. Nucleosides not analysed are shown in red. Figure taken from (106).

Figure 4.

(A) Schematic diagram showing two sides of yeast tRNA^Phe. The positions of two spermine molecules and four magnesium ions are shown as solid black figures. Front side: spermine molecule extends from the D-stem into the anticodon stem. Back side: spermine molecule binds at the junction of the D and acceptor stem, in close proximity to the variable loop. Figure edited from (116). (B) Best conformations for polyamines docked to tRNA (PDB entry 6TNA). Green—the polyamines. tRNA in sphere-filling model with (i) spermidine and (ii) spermine binding sites in sticks. Binding sites for (iii) spermidine and (iv) spermine represented in sticks with the corresponding base residues. Figure edited from (129).