The 4/1 protein was originally isolated in a yeast two-hybrid screening as an interactor of the movement protein of Tomato spotted wilt virus (genus Tospovirus). This is a plant-specific protein with no detectable sequence similarity to any known protein. The GFP-fused 4/1 protein of Nicotiana tabacum (Nt-4/1-GFP) is localized to cytoplasmic bodies, which are non-membrane structures capable of actin dependent movement and associated with the tubular endoplasmic reticulum, endosome-like structures and the plasma membrane. The Nt-4/1 protein has signals directing its shuttling between the cytoplasm and the nucleus. The Nt-4/1 protein binds RNA substrates exhibiting a strong preference for imperfect RNA duplexes. Virus-induced gene silencing of the 4/1 gene in N. benthamiana plants is found to enhance the systemic transport of Potato spindle tuber viroid. On the other hand, a high-level of expression of Nt-4/1 from a Potato virus X vector results in suppressed virus systemic movement. Structure predictions demonstrate that the tertiary structure of 4/1 proteins is strikingly similar to that of yeast protein She2p capable of nucleo-cytoplasmic trafficking, RNA-binding, and actin-dependent directed intracellular transport of specific mRNAs.