KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT.

ABSTRACT: The histone locus body (HLB) is a membraneless organelle that determines the transcription of replication-dependent histones. However, the mechanisms underlying the appropriate formation of the HLB in the nucleus but not in the cytoplasm remain unknown. HLB formation is dependent on the scaffold protein NPAT. We identify KPNA3 as a specific importin that drives the nuclear import of NPAT by binding to the nuclear localization signal (NLS) sequence. NPAT undergoes phase separation, which is inhibited by KPNA3-mediated impairment of self-association. In this, a C-terminal self-interaction facilitator (C-SIF) motif, proximal to the NLS, binds the middle 431-1,030 sequence to mediate the self-association of NPAT. Mechanistically, the anchoring of KPNA3 to the NPAT-NLS sterically blocks C-SIF m

SUBMITTER: Xu SB 

PROVIDER: S-EPMC11613458 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature