Son is Essential for Nuclear Speckle Organization and Cell Cycle Progression

Abstract

<p>Nuclear speckles provide important spatial organization and dynamic regulation for premRNA processing factors in mammalian cells. While the nuclear speckle proteome is complex, little is known at the molecular level about how these factors are organized into nuclear speckles or how alterations in the organization of these factors impacts gene expression. We have discovered a new function for a large (2564 amino acid) nuclear speckle protein called Son in maintaining the organization of pre-mRNA processing factors in nuclear speckles. Depletion of Son by RNAi causes snRNP and serine-arginine rich (SR protein) splicing factors to undergo dramatic disorganization into doughnut-shaped nuclear speckles. Rescue of the disorganized nuclear speckle phenotype requires a region of Son with multiple tandem repeat motifs that are unique to Son. This demonstrates that the tandem repeats of Son are necessary for appropriate localization of pre-mRNA processing factors, and it suggests a potential role for Son as a nuclear speckle scaffold. Son depletion does not alter protein levels of other splicing factors, and it does not reduce global transcription or constitutive splicing. However, Son depletion can affect alternative splice site selection. Surprisingly, in addition to its nuclear functions, Son depletion also results in decreased cell proliferation due to growth arrest in mitosis. Son is critical for promoting the transition from metaphase to anaphase. Son is therefore essential for nuclear organization and function, as well as for normal cell cycle progression.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>