Cryo-EM structure of a transcribing cypovirus

Area of Science:

• Structural Biology
• Virology
• Molecular Biology

Background:

• Double-stranded RNA viruses in the Reoviridae family transcribe and cap messenger RNA (mRNA) within an intact icosahedral capsid.
• The precise mechanism by which viral capsid proteins coordinate mRNA transcription and capping remains largely unknown.
• Cypovirus serves as an excellent model system for investigating these processes in Reoviridae viruses.

Purpose of the Study:

• To elucidate the structural basis of mRNA transcription and capping in transcribing cypovirus.
• To understand the role of viral capsid protein conformational changes in facilitating these essential viral processes.

Main Methods:

• Near-atomic-resolution cryoelectron microscopy was employed to generate a full backbone model of a transcribing cypovirus.
• Comparative structural analysis between transcribing and nontranscribing cypovirus structures.

Main Results:

• Conformational changes in major capsid proteins lead to an enlarged internal capsid chamber, allowing genomic RNA greater flexibility.
• A widened peripentonal channel, identified as the nascent mRNA pathway, revealed a partially resolved mRNA structure.
• Conformational changes in turret proteins created an open turret structure, and a GMP moiety was found in the guanylyltransferase domain, indicating the capping process.

Conclusions:

• The study reveals specific structural adaptations in the cypovirus capsid that facilitate coordinated mRNA transcription and capping.
• These findings provide critical insights into the molecular mechanisms governing RNA virus replication and gene expression within the viral particle.