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Cyclic CMP and cyclic UMP mediate bacterial immunity against phages.

Nitzan Tal1, Benjamin R Morehouse2, Adi Millman1

  • 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.

Cell
|October 13, 2021
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Summary
This summary is machine-generated.

Cyclic pyrimidines 3

Keywords:
Pycsaranti-phagebacteriacCMPcUMPcyclasedefensepb8phagepyrimidine

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Immunology

Background:

  • Cyclic pyrimidines, 3',5'-cyclic cytidine monophosphate (cCMP) and 3',5'-cyclic uridine monophosphate (cUMP), have been identified in various organisms.
  • Unlike well-established cyclic nucleotides like cAMP and cGMP, their biological roles remain largely unknown.
  • Understanding the function of cyclic pyrimidines is crucial for advancing knowledge in cellular signaling and defense mechanisms.

Purpose of the Study:

  • To elucidate the biological function of cyclic pyrimidines (cCMP and cUMP).
  • To investigate the role of cCMP and cUMP as second messengers in bacterial systems.
  • To identify the enzymes responsible for synthesizing these cyclic pyrimidines and their mechanism of action.

Main Methods:

  • Discovery and characterization of bacterial pyrimidine cyclase enzymes.
  • Analysis of cCMP and cUMP synthesis following phage infection.
  • Structural determination of a uridylate cyclase enzyme.
  • Investigation of the activation of immune effectors by cyclic pyrimidines.

Main Results:

  • cCMP and cUMP function as second messengers in bacterial antiviral immunity.
  • A novel family of bacterial pyrimidine cyclase enzymes synthesizes cCMP and cUMP upon phage infection.
  • These cyclic pyrimidines activate immune effectors, initiating an antiviral response.
  • The crystal structure of a uridylate cyclase reveals the mechanism for selective pyrimidine cyclization.

Conclusions:

  • Cyclic pyrimidines (cCMP and cUMP) are key signaling molecules in bacterial innate immunity against viruses.
  • Pyrimidine cyclase systems (Pycsar) are widespread in prokaryotes, highlighting their evolutionary significance.
  • This study clarifies the long-standing mystery surrounding the biological roles of cyclic pyrimidines.