The role of G-quadruplex (G4) RNA structures is multifaceted and controversial. Here, we have used as a model the EBV-encoded EBNA1 and the Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded LANA1 mRNAs. We have compared the G4s in these two messages in terms of nucleolin binding, nuclear mRNA retention, and mRNA translation inhibition and their effects on immune evasion. The G4s in the EBNA1 message are clustered in one repeat sequence and the G4 ligand PhenDH2 prevents all G4-associated activities. The RNA G4s in the LANA1 message take part in similar multiple mRNA functions but are spread throughout the message. The different G4 activities depend on flanking coding and non-coding sequences and, interestingly, can be separated individually. Together, the results illustrate the multifunctional, dynamic and context-dependent nature of G4 RNAs and highlight the possibility to develop ligands targeting specific RNA G4 functions. The data also suggest a common multifunctional repertoire of viral G4 RNA activities for immune evasion.

CNRS UMR9187 INSERM U1196 Institut Curie PSL Research University Orsay France

CNRS UMR9187 INSERM U1196 Université Paris Sud Université Paris Saclay Orsay France

Department of Medical Biosciences Umeå University Umeå Sweden

ICCVS University of Gdańsk Science Gdańsk Poland

Inserm UMR1078 Université de Bretagne Occidentale Bretagne CHRU Brest Brest France

Inserm UMRS1131 Institut de Génétique Moléculaire Université Paris 7 Hôpital St Louis Paris France

ISP INRAE Université de Tours UMR1282 Tours France

RECAMO Masaryk Memorial Cancer Institute Brno Czech Republic

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Abundance of G-Quadruplex Forming Sequences in the Hepatitis Delta Virus Genomes

The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA