Mathematical model of nuclear speckle morphology

Abstract

Nuclear speckles are nuclear bodies consisting of populations of small and irregularly shaped droplet-like molecular condensates that contain various splicing factors. Recent experiments have shown the following morphological features of nuclear speckles: (I) Each molecular condensate contains SON and SRRM2 proteins, and MALAT1 non-coding RNA surrounds these condensates; (II) In the normal interphase of the cell cycle, these condensates are broadly distributed throughout the nucleus in multicellular organisms. In contrast, the fusion of condensates leads to the formation of strongly condensed spherical droplets when cell transcription is suppressed; (III) SON is dispersed spatially in MALAT1 knocked-down cells, whereas MALAT1 is dispersed in SON knocked-down cells by the collapse of nuclear speckles. However, the detailed interactions among molecules that reveal the mechanisms of this rich variety of morphologies remain unknown. In this study, a coarse-grained molecular dynamics model of the nuclear speckle was developed considering the dynamics of SON, SRRM2 or SRSF2, MALAT1, and pre-mRNA as representative components of condensates. The simulations reproduced the abovementioned morphological changes, by which the interaction strength among the representative components of the condensates was predicted.