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Diadenosine Tetraphosphate (Ap4A) in Health and Disease

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Modified Nucleic Acids in Biology and Medicine

Part of the book series: RNA Technologies ((RNATECHN))

Abstract

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.

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Author information

Authors and Affiliations

  1. Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, EinKerem, Jerusalem, 91120, Israel

    Suliman Boulos & Hovav Nechushtan

  2. Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel

    Ehud Razin

  3. Cardiovascular Division, Department of Medicine, and Brigham Regenerative Medicine Center, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Inbal Rachmin

  4. Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02139, USA

    Inbal Rachmin

Authors
  1. Suliman Boulos
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  2. Ehud Razin
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  3. Hovav Nechushtan
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  4. Inbal Rachmin
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Corresponding author

Correspondence to Ehud Razin .

Editor information

Editors and Affiliations

  1. Nanobiomedical Center, Adam Mickiewicz University, Poznań, Poland

    Stefan Jurga

  2. Formerly at Institute of Chemistry and Biochemistry, Free University Berlin, Berlin, Germany

    Volker A. Erdmann (Deceased)

  3. Institute of the Bioorganic Chemistry of the Polish Academy of Sciences, Poznań, Poland

    Jan Barciszewski

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Boulos, S., Razin, E., Nechushtan, H., Rachmin, I. (2016). Diadenosine Tetraphosphate (Ap4A) in Health and Disease. In: Jurga, S., Erdmann (Deceased), V., Barciszewski, J. (eds) Modified Nucleic Acids in Biology and Medicine. RNA Technologies. Springer, Cham. https://doi.org/10.1007/978-3-319-34175-0_9

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