Mismatch binding ligand upregulated back-splicing reaction producing circular RNA in a cellular model

Area of Science:

• Molecular Biology
• RNA Biology
• Chemical Biology

Background:

• Circular RNAs (circRNAs) are formed through a specific RNA splicing process called back-splicing.
• circRNAs have emerged as important molecules with diverse regulatory roles in cells.
• Controlling circRNA biogenesis remains a challenge in molecular biology.

Purpose of the Study:

• To investigate the potential of small molecules to modulate circRNA production.
• To demonstrate a novel method for inducing circRNA synthesis using a chemical compound.

Main Methods:

• Utilized a synthetic small molecule, naphthyridine carbamate dimer (NCD).
• Designed pre-mRNAs with specific NCD-binding sites (UGGAA/UGGAA).
• Assessed circRNA production in cellular models following NCD treatment.

Main Results:

• Naphthyridine carbamate dimer (NCD) significantly upregulated circRNA production from targeted pre-mRNAs.
• The NCD-mediated upregulation was dependent on the presence of the specific UGGAA/UGGAA binding site.
• Demonstrated successful small-molecule induction of circRNA synthesis in cells.

Conclusions:

• Small molecules can be engineered to control circRNA biogenesis.
• NCD represents a promising tool for modulating circRNA levels.
• This work opens avenues for therapeutic applications targeting circRNA pathways.