RNA aptamers for sodium and lithium are abundant in mammals

Riboswitches are common in the bacterial domain of life where they regulate gene expression in response to binding metabolites, elemental ions, or other small ligands. We used comparative sequence analyses to identify numerous RNA motifs in humans and other mammals that are similar in sequence and structure to bacterial riboswitch aptamers for cationic sodium and lithium. Candidates are found in the mRNA transcripts for ~70 genes relevant to ion conductance, neuronal development and function, or to various neurological diseases. Bioinformatic and biochemical analyses support the hypothesis that mammals make extensive use of these RNA aptamers to selectively bind Na⁺ and Li⁺. These structured RNA domains are often located in regions of mRNAs or their putative antisense transcripts that suggest they are components of riboswitches. Such associations also expose links between these alkali metal ions and genes whose expression is likely under monovalent ion regulation. These findings are also consistent with the hypothesis that Li⁺ is a natural contributor to the regulation of genes relevant to certain mental disorders.