Location: ISB 217
Moscow State University, Moscow, Russia; M.Sc.
Brown University, Providence, RI; Ph.D.
We study the importance of spatial organization of regulatory protein/RNA complexes within the cytoplasm. Our model organism is the nematode, C. elegans. C. elegans reproduction is sustained by germ cells that give rise to eggs and sperm. Our lab investigates how the germ cell RNA regulatory machinery is organized in cytoplasmic organelles called P granules (or germ granules). The strategy of assembling important regulators in cytoplasmic foci is conserved across species, and we anticipate that our findings will shed light on the functions of conserved mammalian regulators in development and disease.
FBF-2/germ granule interaction
We found cooperation between germ granules and a RNA regulatory protein FBF-2 (a PUF family member). Other PUFproteins including FBF-2 localize to cytoplasmic RNA granules but the regulation and significance of this localization is unknown. We work on defining the structural features and molecular interactions directing FBF-2 to germ granules. Additionally, we are investigating how the FBF-2 function is regulated by the presence of germ granules.
Structure/function analysis of FBF-2-mediated silencing in tissue culture
To characterize FBF-2 cooperation with germ granule components more precisely in a reconstituted system, studies in the worm are expanded into tissue culture cells. We test whether the ability of FBF-2 to assemble into cytoplasmic granules correlates with its function as a translational repressor.
Identification of mRNAs bound to germ granule components
To broaden our understanding of mRNA targets regulated by germ granules, we plan to identify germ-granule-regulated RNAs by immunoprecipitation of tagged germ granule components and identification of associated mRNA targets on a genome-wide scale by high-throughput RNA sequencing. Based on the sterility phenotype of germ granule component mutants, we expect to identify mRNAs essential for germline development and reproduction, and study their regulation and function. In the long term, genome-scale identification and characterization of relevant RBP targets will build a post-transcriptional gene regulatory network of the germ cells.
Voronina, E. The diverse functions of germline P granules in C. elegans. Mol Reprod Dev 2012; in press
Voronina, E., Paix, A. and Seydoux, G. The P granule component PGL-1 promotes the localization and silencing activity of the PUF protein FBF-2 in germline stem cells. Development 2012; 139(20):3732-3740
Joseph-Strauss, D., Gorjánácz, M., Santarella-Mellwig, R., Voronina, E., Audhya, A., Cohen-Fix, O. Sm protein down-regulation leads to defects in nuclear pore complex disassembly and distribution in C. elegans embryos. Dev Biol 2012; 365(2);445-457.
Voronina, E., Seydoux, G., Sassone-Corsi, P., Nagamori, I. RNA Granules in Germ Cells. In Germ Cells (Eds. Sassone-Corsi, Fuller, Braun). Cold Spring Harb Perspect Biol 2011; 85-111
Voronina, E. and Seydoux, G. The C. elegans homolog of nucleoporin Nup98 is required for the integrity and function of germline P granules. Development 2010; 137(9):1441-1450
Field of Study
RNA regulation in animal development