4.8 Article

A GTP-synthesizing ribozyme selected by metabolic coupling to an RNA polymerase ribozyme

Journal

SCIENCE ADVANCES
Volume 7, Issue 41, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abj7487

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Funding

  1. NASA [NNX16AJ27G]
  2. U.S. Department of Education through the GAANN fellowship [P200A150251]
  3. Roger Tsien Fellowship from the Department of Chemistry and Biochemistry at UCSD
  4. NASA [903008, NNX16AJ27G] Funding Source: Federal RePORTER

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The study demonstrated a catalytic RNA that produces GTP, supporting RNA synthesis in early life forms, which is essential for understanding the mechanism of early life forms.
Synthesis of RNA in early life forms required chemically activated nucleotides, perhaps in the same form of nucleoside 5'-triphosphates (NTPs) as in the contemporary biosphere. We show the development of a catalytic RNA (ribozyme) that generates the nucleoside triphosphate guanosine 5'-triphosphate (GTP) from the nucleoside guanosine and the prebiotically plausible cyclic trimetaphosphate. Ribozymes were selected from 1.6 x 10(14) different randomized sequences by metabolically coupling 6-thio GTP synthesis to primer extension by an RNA polymerase ribozyme within 10(16) emulsion droplets. Several functional RNAs were identified, one of which was characterized in more detail. Under optimized reaction conditions, this ribozyme produced GTP at a rate 18,000-fold higher than the uncatalyzed rate, with a turnover of 1.7-fold, and supported the incorporation of GTP into RNA oligomers in tandem with an RNA polymerase ribozyme. These results are discussed in the context of early life forms.

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