KPNA1/importin α5 localizes to the nucleolus and associates with box C/D snoRNP complexes.

Abstract

KPNA1 (karyopherin α1, also known as importin α5) is a well-characterized nuclear transport factor; however, its functions beyond canonical nuclear transport remain incompletely understood. Here, we show that KPNA1 localizes to the nucleolus in neuronal tissues and is associated with box C/D small nucleolar ribonucleoprotein (snoRNP)-related components, including DDX21, NOP58, NOP56, and fibrillarin (FBL). These associations were largely preserved after nuclease treatment. Loss of KPNA1 is associated with changes in box C/D snoRNA levels. Live-cell imaging and domain-specific analyses of KPNA1 indicate that the importin β1-binding domain contributes to nucleolar localization, whereas the C-terminal region influences nucleolar dynamics. Notably, the schizophrenia-associated KPNA1E448X mutation exhibits aberrant nucleolar accumulation and reduced association with snoRNP-related components. Collectively, these findings provide evidence for a previously unrecognized association between KPNA1 and box C/D snoRNP complexes, thereby extending the functional repertoire of KPNA1 beyond its canonical role in nuclear transport.