Modulating dynamics and function of nuclear actin with synthetic bicyclic peptides

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Actin dynamics (G-actin to F-actin polymerization/depolymerization) are crucial in both cytoplasm and nucleus.
• Nuclear actin regulates gene expression and DNA double-strand break (DSB) repair.
• Existing G-actin-binding molecules are difficult to synthesize and cannot selectively target nuclear actin.

Purpose of the Study:

• To develop and introduce synthetic bicyclic peptides into living cells.
• To investigate the nuclear localization and function of these peptides.
• To explore their potential in manipulating nuclear actin dynamics and functions.

Main Methods:

• Generation of synthetic bicyclic peptides that bind monomeric G-actin.
• Conjugation of bicyclic peptides to a nuclear localization signal (NLS).
• Introduction of NLS-bicyclic peptides into living cells and assessment of nuclear actin.
• Evaluation of effects on transcriptional regulation and DSB repair.

Main Results:

• NLS-bicyclic peptides successfully localized to the nucleus.
• These peptides inhibited the formation of nuclear filamentous actin (F-actin).
• Nuclear F-actin inhibition impaired transcriptional regulation and DSB repair processes.

Conclusions:

• NLS-linked bicyclic peptides can be effectively introduced into the nucleus.
• These peptides offer a tool to specifically manipulate nuclear actin dynamics.
• This approach has implications for understanding and potentially modulating nuclear actin-dependent cellular processes.