Current research on viral proteins that interact with fibrillarin.

The nucleolus is a multifunctional nuclear domain primarily dedicated to ribosome biogenesis. Certain viruses developed strategies to manipulate host nucleolar proteins to facilitate their replication by modulating ribosomal RNA (rRNA) processing. This association interferes with nucleolar functions resulting in overactivation or arrest of ribosome biogenesis, induction or inhibition of apoptosis, and affecting stress response. The nucleolar protein fibrillarin (FBL) is an important target of some plant and animal viruses. FBL is an essential and highly conserved S-adenosyl methionine (SAM) dependent methyltransferase, capable of rRNA degradation by its intrinsically disordered region (IDR), the glycine/arginine-rich (GAR) domain. It forms a ribonucleoprotein complex that directs 2'-O-methylations in more than 100 sites of pre-rRNAs. It is involved in multiple cellular processes, including initiation of transcription, oncogenesis, and apoptosis, among others. The interaction with animal viruses, including human viruses, triggered its redistribution to the nucleoplasm and cytoplasm, interfering with its role in pre-rRNA processing. Viral-encoded proteins with IDRs as nucleocapsids, matrix, Tat protein, and even a viral snoRNA, can associate with FBL, forcing the nucleolar protein to undergo atypical functions. Here we review the molecular mechanisms employed by animal and human viruses to usurp FBL functions and the effect on cellular processes, particularly in ribosome biogenesis.

Plant viral proteins and fibrillarin: the link to complete the infective cycle.

The interaction between viruses with the nucleolus is already a well-defined field of study in plant virology. This interaction is not restricted to those viruses that replicate in the nucleus, in fact, RNA viruses that replicate exclusively in the cytoplasm express proteins that localize in the nucleolus. Some positive single stranded RNA viruses from animals and plants have been reported to interact with the main nucleolar protein, Fibrillarin. Among nucleolar proteins, Fibrillarin is an essential protein that has been conserved in sequence and function throughout evolution. Fibrillarin is a methyltransferase protein with more than 100 methylation sites in the pre-ribosomal RNA, involved in multiple cellular processes, including initiation of transcription, oncogenesis, and apoptosis, among others. Recently, it was found that AtFib2 shows a ribonuclease activity. In plant viruses, Fibrillarin is involved in long-distance movement and cell-to-cell movement, being two highly different processes. The mechanism that Fibrillarin performs is still unknown. However, and despite belonging to very different viral families, the majority comply with the following. (1) They are positive single stranded RNA viruses; (2) encode different types of viral proteins that partially localize in the nucleolus; (3) interacts with Fibrillarin exporting it to the cytoplasm; (4) the viral protein-Fibrillarin interaction forms an RNP complex with the viral RNA and; (5) Fibrillarin depletion affects the infective cycle of the virus. Here we review the relationship of those plant viruses with Fibrillarin interaction, with special focus on the molecular processes of the virus to sequester Fibrillarin to complete its infective cycle.