A Novel Function for the Sm Proteins in Germ Granule Localization during C. elegans Embryogenesis

Abstract

General mRNA processing factors are traditionally thought to function only in the control of global gene expression. Here we show that the Sm proteins, core components of the splicesome, also regulate germ granules during early C. elegans development. Germ granules are large cytoplasmic particles that localize to germ cells and their precursors during embryogenesis of diverse organisms. In C. elegans, germ granules, called P granules, are segregated to the germline precursor cells during embryogenesis by asymmetric cell division, and they remain in germ cells at all stages of development. We found that at least some Sm proteins are components of P granules. Moreover, disruption of Sm activity caused defects in P granule localization to the germ cell precursors during early embryogenesis. In contrast, loss of other splicing factor activities had no effect on germ granule control in the embryo. These observations suggest that the Sm proteins control germ granule integrity and localization in the early C. elegans embryo and that this role is independent of pre-mRNA splicing. Thus, a highly conserved splicing factor may have been adapted to control both snRNP biogenesis and the localization of components important for germ cell function.

A Genomewide RNAi Screen for Genes That Affect the Stability, Distribution and Function of P Granules in Caenorhabditis elegans

“…However, previous RNAi depletion of other splicing components did not disrupt P-granule patterns in embryos (Barbee et al 2002), suggesting that P-granule integrity and perinuclear localization in embryonic cells do not depend on pre-mRNA splicing. Our screen demonstrated that at least some pre-mRNA splicing factors are necessary for proper PGL-1 localization to granules at the nuclear periphery in embryos.…”

“…Sm components of the splicesome have been shown to localize to germ plasm in multiple species, and previous RNAi depletion of the C. elegans Sm proteins disrupted P-granule patterns in embryos (Moussa et al 1994;Barbee et al 2002;Chuma et al 2003;Bilinski et al 2004;Barbee and Evans 2006). However, previous RNAi depletion of other splicing components did not disrupt P-granule patterns in embryos (Barbee et al 2002), suggesting that P-granule integrity and perinuclear localization in embryonic cells do not depend on pre-mRNA splicing.…”

“…Nascent transcripts are processed in the nucleus by spliceosomes prior to their export as mature mRNAs. Sm proteins are core components of nuclear spliceosomes and are also concentrated in the cytoplasmic germ granules of multiple species (Moussa et al 1994;Chuma et al 2003;Barbee et al 2002;Bilinski et al 2004). In C. elegans, Sm proteins are required for proper P-granule localization to the nuclear periphery; it has been proposed that this role is independent of premRNA splicing (Barbee and Evans 2006).…”

“…Targeted studies have demonstrated that mutation or RNAi of other genes also disrupts PGL-1 in the germ line. These include genes encoding the nuclear transportins IMB-2, IMB-3, IMB-5, and IMA-3 ( J. Ahringer, personal communication; Geles and Adam 2001); the maternal zinc finger protein MEX-1 (Mello et al 1992;Guedes and Priess 1997); many of the Sm spliceosome components (Barbee et al 2002); the eIF-5A homolog IFF-1 (Hanazawa et al 2004); the germ-line enriched protein MEG-1 (Leacock and Reinke 2008); and the oocyte maturation factors OMA-1 and OMA-2 (Shimada et al 2006). Of these, MEX-1, MEG-1, OMA-1, and the Sm proteins are also P-granule components.…”

TACC1–chTOG–Aurora A protein complex in breast cancer

“…The TACCchTOG-Aurora or TACC-chTOG-PCTAIRE complex(es) may serve several functions, including one during cell division. Another role might be in the establishment or maintenance of cell polarity (Richter, 2001); a role for Taxin-associated complexes in asymmetric cell division is also possible (Barbee et al, 2002;Berdnik and Knoblich, 2002); this might be one explanation of the hematopoietic stem cell defects in Tacc3 deficient mice (Piekorz et al, 2002). TACC1 might also participate in the regulation of cytokinesis and interact at the midbody with another molecular complex, including instead of Aurora A the midbodyassociated Aurora B kinase, or another mitotic kinase such as a Polo kinase.…”