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- Title
Nucleolin Regulates the Expression of Kaposi's Sarcoma-Associated Herpesvirus' Latency-Associated Nuclear Antigen through G-Quadruplexes in the mRNA.
- Authors
Zareie, Andrew R.; Verma, Subhash C.
- Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) establishes life-long latent infection and is linked to several human malignancies. Latency-associated nuclear antigen (LANA) is highly expressed during latency, and is responsible for the replication and maintenance of the viral genome. The expression of LANA is regulated at transcriptional/translational levels through multiple mechanisms, including the secondary structures in the mRNA sequence. LANA mRNA has multiple G-quadruplexes (G4s) that are bound by multiple proteins to stabilize/destabilize these secondary structures for regulating LANA. In this manuscript, we demonstrate the role of Nucleolin (NCL) in regulating LANA expression through its interaction with G-quadruplexes of LANA mRNA. This interaction reduced LANA's protein expression through the sequestration of mRNA into the nucleus, demonstrated by the colocalization of G4-carrying mRNA with NCL. Furthermore, the downregulation of NCL, by way of a short hairpin, showed an increase in LANA translation following an alteration in the levels of LANA mRNA in the cytoplasm. Overall, the data presented in this manuscript showed that G-quadruplexes-mediated translational control could be regulated by NCL, which can be exploited for controlling KSHV latency.
- Subjects
KAPOSI'S sarcoma-associated herpesvirus; GENE expression; NUCLEOLIN; MESSENGER RNA; LATENT infection
- Publication
Viruses (1999-4915), 2023, Vol 15, Issue 12, p2438
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v15122438