JNK activation dynamics drive distinct gene expression patterns over time mediated by mRNA stability

Area of Science:

• Cellular Biology
• Molecular Biology
• Biochemistry

Background:

• c-Jun N-terminal kinase (JNK) is crucial for regulating cell death.
• JNK activation dynamics influence cell survival versus cell death decisions under stress.
• The link between JNK dynamics and downstream gene expression patterns is not fully understood.

Purpose of the Study:

• To investigate how specific temporal dynamics of JNK activation impact downstream gene expression.
• To explore the role of JNK dynamics in regulating transcription factors like c-Jun.
• To elucidate the contribution of JNK dynamics to cellular responses to stress.

Main Methods:

• Utilized anisomycin to induce sustained, transient, or pulsed JNK activation.
• Assessed downstream gene expression patterns in response to varying JNK activation dynamics.
• Employed ordinary differential equation (ODE) models to analyze gene expression patterns.
• Examined mRNA stability and decay rates.

Main Results:

• Distinct gene expression patterns emerged based on JNK activation dynamics.
• ODE models indicated that mRNA stability mediates a subset of these gene expression clusters.
• Experimental data on mRNA decay rates supported the role of mRNA stability.
• Specific gene clusters were enriched in cell death and inflammatory signaling pathways.

Conclusions:

• JNK activation dynamics significantly shape downstream gene expression profiles.
• mRNA stability is a key mechanism by which JNK dynamics regulate gene expression.
• JNK dynamics play a differential role in regulating cell death and inflammatory pathways.
• These findings add to the understanding of JNK's role in cellular stress responses.