In yeast there are at least 14 members of the beta-karyopherin protein family 
that govern the movement of a diverse set of cargoes between the nucleus and 
cytoplasm. Knowledge of the cargoes carried by each karyopherin and insight into 
the mechanisms of transport are fundamental to understanding constitutive and 
regulated transport and elucidating how they impact normal cellular functions. 
Here, we have focused on the identification of nuclear import cargoes for the 
essential yeast beta-karyopherin, Kap121p. Using an overlay blot assay and 
coimmunopurification studies, we have identified 30 putative Kap121p cargoes. 
Among these were Nop1p and Sof1p, two essential trans-acting protein factors 
required at the early stages of ribosome biogenesis. Characterization of the 
Kap121p-Nop1p and Kap121p-Sof1p interactions demonstrated that, in addition to 
lysine-rich nuclear localization signals (NLSs), Kap121p recognizes a unique 
class of signals distinguished by the abundance of arginine and glycine residues 
and consequently termed rg-NLSs. Kap104p is also known to recognize rg-NLSs, and 
here we show that it compensates for the loss of Kap121p function. Sof1p is also 
transported by Kap121p; however, its import can be mediated by a piggyback 
mechanism with Nop1p bridging the interaction between Sof1p and Kap121p. 
Together, our data elucidate additional levels of complexity in these nuclear 
transport pathways.