Sm proteins specify germ cell fate by facilitatingoskarmRNA localization

Abstract

SUMMARYSm and Sm-like proteins are RNA-binding factors found in all three domains of life. Eukaryotic Sm proteins play essential roles in pre-mRNA splicing, forming the cores of spliceosomal small nuclear ribonucleoproteins (snRNPs). Recently, Sm proteins have been implicated in the specification of germ cells. However, a mechanistic understanding of their involvement in germline specification is lacking and a germline-specific RNA target has not been identified. We demonstrate that Drosophila SmB and SmD3 are specific components of the oskar messenger ribonucleoprotein (mRNP), proper localization of which is required for establishing germline fate and embryonic patterning. Importantly, oskar mRNA is delocalized in females harboring a hypomorphic mutation in SmD3, and embryos from mutant mothers are defective in germline specification. We conclude that Sm proteins function to establish the germline in Drosophila, at least in part by mediating oskar mRNA localization.

RNA Granules in Germ Cells

“…In addition to perinuclear nuage, nurse cells and the oocyte contain sponge bodies, which are stacks of endoplasmic reticulum (ER) cisternae embedded in an electron-dense matrix scattered through the cytoplasm (Fig. 1C) Hay et al 1988;Liang et al 1994Gruidl et al 1996aIkenishi et al 1996Bilinski et al 2004Knaut et al 2000Toyooka et al 2000Castrillon et al 2000 Argonaute Barbee et al 2002Bilinski et al 2004Moussa et al 1994Chuma et al 2003Anne 2010Gonsalvez et al 2010 Kotaja et al 2006b SnRNP Essential component of the spliceosomal complex that function in pre-mRNA processing Paniagua et al 1985;Moussa et al 1994;Biggiogera et al 1990 GRTH Dead box RNA helicase that is required for spermatogenesis. Deficient of GRTH shows impaired CB formation (Wilsch-Brauninger et al 1997).…”

“…In Drosophila, sDMA modifications of the Argonaute Aubergine are recognized by Tudor, and are necessary for Aubergine-Tudor interaction and germ granule assembly (Anne et al 2007;Kirino et al 2009;Nishida et al 2009). sDMA modifications of the spliceosomal Sm proteins SmB and SmD3 also depend on Capsuleen/Valois, and are required for their localization to germ granules; however, the relevant Tudor-domain partners of these proteins have not been identified (Anne 2010;Gonsalvez et al 2010). In the mouse, several Tudor domain proteins interact with the sDMA-modified Piwi family Argonautes and are required for spermatogenesis (reviewed in Arkov and Ramos 2010;Vourekas et al 2010).…”

SmD3 Regulates Intronic Noncoding RNA Biogenesis

“…Unlike SmD3 haploinsufficient cells, SmB knockdown cells remain sensitive to palmitate-induced death, suggesting that SmD3 has a function distinct from those of other Sm protein family members. Additionally, SmD3 has been observed to function independently of the Sm core in the cytoplasm (12). SmD3 has also been previously shown to bind small Cajal body RNAs (scaRNAs), a class of snoRNAs specifically localizing to Cajal bodies, and human telomerase (hTR) via a CAB box site (11).…”

Genetics of germ cell development

“…[15][16][17] Induction of the germline in mouse. In the mouse, all cells in the embryo are capable of contributing to the germline until after the blastocyst stage, indicating that there is no specific germ cell lineage predetermined by maternally inherited cytoplasmic factors.…”