ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability.

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• Adenosine deaminases acting on RNA (ADARs) modify double-stranded RNA (dsRNA) by converting adenosine to inosine.
• ADAR1 is crucial for immune homeostasis, while ADAR2 is prevalent in the brain and vascular system.
• The RNA exosome complex is vital for RNA processing, turnover, and surveillance.

Purpose of the Study:

• To investigate the interactome of ADAR2.
• To identify shared interaction partners between ADAR1 and ADAR2.
• To elucidate the functional consequences of ADAR-exosome complex interactions.

Main Methods:

• Investigated the ADAR2 interactome and its overlap with ADAR1.
• Utilized immunoprecipitation to validate ADAR-exosome interactions in multiple cell lines.
• Employed an MS2-MCP tethering system to assess RNA stability and utilized EXOSC3 depletion and ADAR knockdown experiments.

Main Results:

• Uncovered a shared interaction network between ADAR1, ADAR2, and RNA exosome components within the nucleus.
• Demonstrated that ADAR recruitment to reporter transcripts decreases RNA stability via the RNA exosome complex.
• Showed that ADARs' interaction with the RNA exosome complex is essential for proper rRNA processing.

Conclusions:

• ADAR1 and ADAR2 interact with the RNA exosome complex, influencing RNA stability and processing.
• This interaction is critical for maintaining cellular RNA homeostasis and innate immune responses.
• Disruption of ADAR-exosome interactions leads to cellular consequences, including perturbed rRNA processing.