Microtubules are organized by the centrosome, a dynamic organelle that exhibits changes in both size and number during the cell cycle. The maintenance of appropriate centrosome size is critical for proper cell division and partitioning of biomolecules and organelles between the daughter cells. However the exact mechanism by which this process is regulated is unclear.
In a collaborative study with Dr. Kevin O'Connell of the NIDDK, we showed that SZY-20, a predicted RNA-binding protein, plays a critical role in limiting centrosome size in the nematode worm C. elegans. Homologs of SZY-20 are present throughout eukaryotes pointing to conserved role for this protein. SZY-20 localizes in part to centrosomes and in its absence centrosomes possess increased levels of centriolar and pericentriolar components including gamma-tubulin and the centriole duplication factors ZYG-1 and SPD-2. These enlarged centrosomes possess normal centrioles, nucleate more microtubules, and fail to properly direct a number of microtubule-dependent processes. Depletion of ZYG-1 restores normal centrosome size and function to szy-20 mutants, whereas loss of szy-20 suppresses the centrosome duplication defects in both zyg-1 and spd-2 mutants. Our results thus describe a pathway that determines centrosome size and implicate centriole duplication factors in this process. Computational analysis showed that SZY-20 contains a two novel protein domains the SUZ and SUZ-C domain which are predicted to be respectively critical for RNA-binding and targeting of ribonucleoprotein complexes. It was also shown to be a part of a large complex of RNA-binding proteins. Mutagenesis of conserved residues in these domains result in loss of SZY-20 function and loss of ability for form RNA-protein complexes. The presence of a RNA-binding domain in SZY-20, a centrosomal protein, suggests that it might be key for partitioning of RNA during cell division.
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