Two RNA Folds from One Sequence: A Ribozyme with Versatile Substrate Processing Abilities.

Area of Science:

• Biochemistry
• Molecular Biology
• RNA Science

Background:

• Ribozymes are RNA molecules with catalytic activity.
• RNA molecules can adopt complex structures and perform various functions.
• Understanding RNA conformational flexibility is key to understanding early life evolution.

Purpose of the Study:

• To design a single RNA sequence with dual catalytic functions (cleavage and ligation).
• To investigate the conformational flexibility of RNA molecules.
• To explore the implications of RNA conformational adaptability for the origin of functional folds.

Main Methods:

• Designing a single RNA sequence capable of adopting two distinct ribozyme folds.
• Experimentally demonstrating RNA cleavage and ligation activities of the designed RNA.
• Utilizing a one-pot reaction to show combined catalytic functions.

Main Results:

• A single RNA sequence, termed chameleon ribozyme (CHR), was successfully designed.
• CHR demonstrated efficient catalytic cleavage of two different substrates.
• CHR also showed efficient RNA ligation, and both activities were observed in a one-pot reaction.
• Sequence variants of hairpin and hammerhead ribozymes were found to intersect.

Conclusions:

• Short RNA molecules can possess significant conformational flexibility.
• The chameleon ribozyme exhibits adaptability to environmental cues, switching between catalytic functions.
• This conformational flexibility is a vital characteristic for the emergence of novel functional folds in early RNA-based life.