Characterization of nucleolar localization and exclusion signals in terminal deoxynucleotidyltransferase interacting factor 2/estrogen receptor a-binding protein

Terminal deoxynucleotidyltransferase interacting factor 2/estrogen receptor a-binding protein (TdIF2/ERBP) is a multifunctional nucleolar protein. The nucleolar localization of TdIF2/ ERBP is important for its functions because it promotes ribosomal RNA transcription. However, signal sequences that direct TdIF2/ERBP to the nucleolus are not well characterized. We examined the TdIF2/ERBP sequence using truncation and mutation analyses to determine whether the nucleosome binding and C-terminal domains of TdIF2/ERBP possess nucleolar localization signals (NoLSs). In these domains, four NoLSs that could direct the mCherry protein to the nucleolus were detected. In addition, a short stretch of hydrophobic residues (VLLVL) in the center of TdIF2/ERBP acted as a nucleolar exclusion signal, which reduced the nucleolar accumulation of mCherry-NoLS fusion proteins. These results would contribute to improving the prediction of NoLSs from protein sequences. The short, transferrable localization signals would be valuable tools for understanding the association between localization and functions of nucleolar proteins.