Role of Importin and Ran in Nuclear Import of Histones

Histones H2A, H2B, H3, and H4 are called the core histones and two copies of H2A-H2B dimers and a copy of (H3-H4)2 tetramer make up the histone octamer. Histone proteins are important to compact the genomic DNA. Like most proteins, histones are transcribed in the cytoplasm and need to be imported into the nucleoplasm where they function. Import of cargo involves Importins, and Rans. Importins transport cargo from the cytoplasm to the nucleus. When this binary complex reaches the nucleus, it binds with RanGTP and this causes the release of cargo. It is not precisely known how Importins and Rans import histones. The work of Padavannil et al. (2019) suggests that the Importin and Ran import histones in a non-canonical way into the nucleus. When nuclear import does not function correctly, it leads to various cancers and developmental disorders, highlighting a need to understand the nuclear transport processes. Here, we aim to study these proteins and uncover the mechanism behind the nuclear transport of H2A-H2B using hydrogen- deuterium exchange mass spectrometry. We find that addition of Ran destabilizes two of the H2A- H2B-binding surfaces on Imp9 and stabilizes one interface. This indicates that the N-terminal heat repeats and acidic loop of Imp9 are responsible for the formation of the unconventional ternary complex containing Imp9, H2A-H2B, and Ran.