The NF90 family of double-stranded RNA binding proteins is generated by alternative splicing of transcripts from the ILF3 gene. Members of this family have been found in several different subcellular locations and interact with varied protein complexes, suggestive of functions in various cellular processes including gene expression, DNA replication and repair, cell growth, and the anti-viral immune response. Although at least 7 unique protein products have been predicted from the cDNAs, it has been established that four family members predominate in human cell lines and that these isoforms exhibit different levels of activity in transient expression assays. These observations raise the possibility that the isoforms participate in specific complexes that display distinct functions within cells. To address this hypothesis, native NF90 containing complexes will be isolated from recently developed, well-characterized stable cell-lines expressing the four isoforms. The composition of the complexes will be established using proteomic techniques. Once the complex compositions are known for asynchronous human cells (Aim 1), a similar approach will be used to investigate the dynamics of the complexes containing different NF90 members as a function of cell cycle phase and viral infection (Aim 2).