A viral nuclear noncoding RNA binds re-localized poly(A) binding protein and is required for late KSHV gene...

Area of Science:

• Virology
• Molecular Biology
• RNA Biology

Background:

• Gamma herpesviruses, like Kaposi's Sarcoma-Associated Herpesvirus (KSHV), express abundant nuclear noncoding RNAs during infection.
• The function of the polyadenylated nuclear (PAN) RNA during KSHV lytic infection remains largely unknown.
• Host poly(A)-binding protein C1 (PABPC1) typically functions in the cytoplasm to regulate mRNA stability and translation.

Purpose of the Study:

• To elucidate the function of KSHV PAN RNA during the viral lytic cycle.
• To investigate the interaction between PAN RNA, PABPC1, and viral protein production.
• To understand the role of PAN RNA in KSHV-mediated host shutoff.

Main Methods:

• Utilized RNase H-targeting antisense oligonucleotides to deplete PAN RNA.
• Performed transient transfection experiments to assess SOX protein effects on PAN RNA levels.
• Investigated PABPC1 re-localization and host shutoff effects in KSHV-infected cells.

Main Results:

• PAN RNA avidly binds to host PABPC1, which is re-localized to the nucleus during KSHV lytic infection.
• SOX protein upregulates PAN RNA levels, dependent on its host shutoff and PABPC1 re-localization functions.
• Depletion of PAN RNA inhibits the production of late viral proteins from polyadenylated viral mRNAs.

Conclusions:

• PAN RNA is essential for the production of late viral proteins during KSHV lytic infection.
• This study identifies a novel mechanism for nuclear noncoding RNAs in gamma herpesvirus pathogenesis.
• The findings expand the known functions of long noncoding RNAs in viral replication.