A cytomegalovirus-encoded lncRNA blocks cell-cycle progression

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Human cytomegalovirus (HCMV) infection leads to abundant viral transcripts, including long non-coding RNA RNA2.7.
• The precise function of HCMV RNA2.7 during infection has remained largely unknown.

Purpose of the Study:

• To elucidate the function of HCMV RNA2.7 in modulating host gene expression and promoting viral propagation.
• To investigate the mechanism by which RNA2.7 influences host cell processes and viral replication.

Main Methods:

• RNA sequencing to analyze global gene expression changes.
• Metabolic labeling of newly synthesized RNA to track RNA dynamics.
• Ribosome profiling to assess translation activity.

Main Results:

• RNA2.7 stabilizes numerous host messenger RNAs (mRNAs) by sequestering RNA-binding proteins, altering the cellular transcriptome.
• RNA2.7 is crucial for HCMV-induced cell-cycle arrest at the G1-S transition, particularly in G1-phase cells.
• Expression of RNA2.7 alone is sufficient to impede cell-cycle progression, with a polyadenosine stretch identified as critical for this function.

Conclusions:

• HCMV RNA2.7 promotes viral replication by enhancing host mRNA stability and inducing cell-cycle arrest.
• RNA2.7 actively reshapes the cellular environment to favor HCMV propagation.