A Threose Nucleic Acid Enzyme with RNA Ligase Activity

Area of Science:

• Origin of Life Studies
• Synthetic Biology
• Biochemistry

Background:

• Threose nucleic acid (TNA) is a simpler alternative nucleic acid to RNA.
• TNA exhibits base-pairing properties and may have preceded RNA in early life.
• Catalytic TNA sequences could have facilitated the transition to the RNA world.

Purpose of the Study:

• To isolate and characterize TNA enzymes with RNA ligase activity.
• To explore TNA's potential as a pre-RNA genetic polymer.
• To develop TNA-based molecular tools for biotechnology.

Main Methods:

• Isolation of RNA ligase TNA enzymes using in vitro selection.
• Characterization of the catalytic activity of the TNA enzyme T8-6.
• Assessment of TNA enzyme substrate specificity and ligation efficiency.

Main Results:

• The TNA enzyme T8-6 was isolated, exhibiting RNA ligase activity.
• T8-6 catalyzes the formation of a 2'-5' phosphoester bond with a kobs of 1.1 × 10^-2 min^-1.
• T8-6 efficiently ligates RNA substrates requiring a UA|GA junction and enables the synthesis of functional RNAs like hammerhead ribozymes.

Conclusions:

• Experimental evidence supports TNA as a plausible pre-RNA genetic polymer.
• TNA enzymes offer a novel molecular tool for biotechnological applications.
• This study provides insights into the transition from TNA to the RNA world.