Fam118B, a novel component in Cajal bodies, is required for Cajal body formation, snRNP biogenesis and cell viability

Abstract

Cajal bodies (CBs) are specialized and dynamic compartments in nucleus that are involved in small nuclear ribonucleoprotein (snRNP) biogenesis. Because of the dynamic and multifunctional roles of CBs, it is of great interest to identify components in CBs to better understand their functions. We performed a genome-wide screen to identify proteins that co-localize with Coilin, the CB marker protein. In this study, we identified and characterized Fam118B as a novel component of CBs. Fam118B is widely expressed in a variety of cell lines derived from various origins. Overexpression of Fam118B changes the canonical morphology of CBs, whereas depletion of Fam118B disrupts the localization of CB components, including Coilin, the survival of motor neuron protein (SMN) and the Sm protein D1 (SmD1). Moreover, depletion ofFam118B reduces splicing capacity and inhibits cell proliferation. In addition, Fam118B associates with Coilin and SMN proteins. Fam118B depletion reduces symmetric dimethylarginine modification of SmD1, which in turn diminishes SMN binding to this Sm protein. Taken together, these data indicate that Fam118B, by regulating SmD1 symmetric dimethylarginine modification, plays an important role in CB formation, snRNP biogenesis and cell viability.