A38
An RNA-protein complex containing Misu (NSun2) is required for mitotic spindle integrity
Shobbir Hussain, Sandra Blanco-Benavente, Michaela Frye
Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, UK
Faithful segregation of chromosomes during eukaryotic cell division is dependent on the correct formation of the mitotic apparatus. Although many factors that regulate mitotic spindle assembly have been identified, an exact understanding of the process is lacking.
We demonstrate that Misu, a novel RNA methyltransferase, is associated with mitotic microtubule as an RNA-protein complex. We also show that Misu interacts with 18S ribosomal RNA in vivo and both the presence of RNA and Misu is essential for correct spindle assembly. Knockdown of Misu using RNAi caused multiple mitotic defects including formation of unstructured spindles, multipolar spindles and chromosome mis-segregation. These defects finally caused aneuploidy and cell death. We conclude that both Misu protein and its RNA substrate are required for proper segregation of chromosomes in metaphase, as well as control key aspects of apoptosis.
These studies reveal novel direct roles for RNA and RNA-protein complexes in the assembly of the spindle apparatus, a structure previously considered to consist only of DNA and proteins. The deployment of RNA-protein complexes to maintain the stability of the spindle might offer novel opportunities as drug targets.
