Diadenosine Tetraphosphate (Ap4A) in Health and Disease

  • Suliman Boulos
  • Ehud RazinEmail author
  • Hovav Nechushtan
  • Inbal Rachmin
Part of the RNA Technologies book series (RNATECHN)


Diadenosine oligophosphates (ApnAs) were initially discovered more than 50 years ago. This group of molecules form a class of compounds derived from ATP and consist of two adenosine molecules bridged by up to six phosphate groups. The first enzymatic production of these compounds was noted by Zamecnik and colleagues in their study with purified lysyl tRNA synthetase (KARS) in mammalian cells.

Multiple studies on the role of ApnAs have been published during the years following their initial discovery. However, technical difficulties hampered some of the studies, and the field has been abandoned for nearly 20 years, until the use of new molecular methods inspired new studies into the functional aspects of these nucleotides in bacterial and eukaryotic systems.

In this chapter, we will discuss the role of ApnAs in prokaryotic and eukaryotic cells and will focus on the most investigated member of the ApnAs family, namely diadenosine tetraphosphate (Ap4A), and its role in a variety of tissues such as the heart and blood vessels, neurons, spermatocytes, neutrophils, and pancreatic cells.

We conclude our chapter with a description of a putative cell signaling pathway involving KARS, whose structure can be modulated so that it is no longer involved in translation but mainly in transcription, through its ability to produce the second messenger Ap4A.


ApnAs: diadenosine oligophosphates Ap3A: diadenosine triphosphate Ap4A: diadenosine tetraphosphate KARS: lysyl-tRNA-synthetase 


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Suliman Boulos
    • 1
  • Ehud Razin
    • 2
    Email author
  • Hovav Nechushtan
    • 1
  • Inbal Rachmin
    • 3
    • 4
  1. 1.Sharett Institute of OncologyHadassah-Hebrew University Medical CenterJerusalemIsrael
  2. 2.Department of Biochemistry and Molecular BiologyInstitute for Medical Research Israel-Canada, The Hebrew University of JerusalemJerusalemIsrael
  3. 3.Cardiovascular Division, Department of Medicine, and Brigham Regenerative Medicine CenterBrigham and Women’s HospitalBostonUSA
  4. 4.Harvard Stem Cell Institute and Department of Stem Cell and Regenerative BiologyHarvard UniversityCambridgeUSA

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