The mysterious diadenosine tetraphosphate (AP4A)

Abstract

Dinucleoside polyphosphates, a class of nucleotides found amongst all the Trees of Life, have been gathering a lot of attention in the past decades due to their putative role as cellular alarmones. In particular, diadenosine tetraphosphate (AP4A) has been widely studied in bacteria facing various environmental challenges and has been proposed to be important for ensuring cellular survivability through harsh conditions. Here, we discuss the current understanding of AP4A synthesis and degradation, protein targets, their molecular structure where possible, insights into the molecular mechanisms of AP4A action and its physiological consequences. Lastly, we will briefly touch on what is known with regards to AP4A beyond the Bacterial Kingdom, given its increasing appearance in the Eukaryotic world. Altogether, the notion that AP4A is a conserved second messenger in organisms ranging from bacteria to humans and is able to signal and modulate cellular stress regulation seems promising.

If the 5’ cap fits (wear it) – Non-canonical RNA capping

“…Dinucleoside polyphosphates (Np n Ns) are another type of molecule similar to the m 7 G RNA cap in structure and just like NAD and the other metabolites serving as RNA caps, they are present in all cells across all domains of life [ 118 ]. They are often called alarmones because their production increases under various stress conditions and their roles range from second messengers to regulators of cellular biosynthetic pathways [ 119 , 120 ].…”