oskar (gene)
| Maternal effect protein oskar | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | |||||||
| Symbol | osk | ||||||
| UniProt | P25158 | ||||||
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oskar is a gene required for the development of the Drosophila embryo. It defines the posterior pole during early embryogenesis. Its two isoforms, short and long, play different roles in Drosophila embryonic development. oskar was named after the main character from the Günter Grass novel The Tin Drum, who refuses to grow up.[1]
Evolutionary history
oskar displays a unique evolutionary origin resulting from a Horizontal Domain Transfer from a probably bacterial endosymbiont onto an ancestral insect genome. The OSK domain is of bacterial origin and fused with the LOTUS domain through a linker domain.[2] This event must have happened just prior to the divergence with the Crustacean, the insect's sister group, as oskar can be found as early as the Zygentoma but does not seem to exist in Crustacean.[3]
Translational-level regulation
oskar is translationally repressed prior to reaching the posterior pole of the oocyte by Bruno, which binds to three bruno response elements (BREs) on the 3' end of the transcribed oskar mRNA.[4] The Bruno inhibitor has two distinct modes of action: recruiting the Cup eIF4E binding protein, which is also required for oskar mRNA localization due to interactions with the Barentsz microtubule-linked transporter,[5] and promoting oligomerization of oskar mRNA.[6] Oskar mRNA harbours a stem-loop structure in the 3’UTR, called the oocyte entry signal (OES), that promotes dynein-based mRNA accumulation in the oocyte.[7]
P granule formation
oskar plays role in recruiting other germ line genes to the germ plasm for PGC (primordial germ cell) specification. oskar mRNA locates to the posterior end of an oocyte and, once translated, the short isoform of oskar (Short oskar) recruits germ plasm components such as the protein Vasa and the RNA-binding proteins of the Piwi family, among many others.[8] The long isoform of oskar (Long oskar) has been implicated in creating an actin network on the posterior pole end.
A second role has been discovered that relates to the formation of P granules, or germ granules. These ribonucleoprotein granules are found in every species' germ line cells. Although they are mobile, they typically localize to the nuclei and sit on nuclear pores. This positioning makes them ideal mRNA regulators, as the mRNA must pass through to exit the nucleus.[9] Translational regulation also makes sense due to the granules' close association with ribosomes. These P granules are phase-transition entities, which means that they can display both liquid-like and hydrogel-like properties.[8] This allows them to be very versatile structures, able to dissolve, condense, and exchange their protein content with their environment at will. Recent studies have shown that the short isoform of oskar has another function as the nucleator of nuclear germ granules. oskar recruits vasa to these round granules, then promotes the localization to the nucleus. oskar was ablated to explore the function of these nuclear germ granules. The results showed that the division of PGCs was compromised without oskar, meaning that the P granules play a role in the cell cycle of germ cells.[8] It is still unclear exactly how the nuclear granules interact with certain factors and what factors (proteins, regulators, inhibitors) they interact with in order to regulate cell division.
Domain families
| OSK | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | OSK | ||||||||
| Pfam | PF17182 | ||||||||
| InterPro | IPR033447 | ||||||||
| CATH | 5a4a | ||||||||
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| OST-HTH/LOTUS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | OST-HTH | ||||||||
| Pfam | PF12872 | ||||||||
| InterPro | IPR025605 | ||||||||
| PROSITE | PS51644 | ||||||||
| CATH | 5a48 | ||||||||
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oskar contains two RNA-binding protein domains: the OSK RNA-binding domain and the OST-HTH/LOTUS domain. The former is structurally related to SGNH hydrolases but lack the active site residues. The latter is a winged helix-turn-helix domain also found in human TDRD5/TDRD7. The OST-HTH domain in oskar is mainly responsible for recruiting the Vasa helicase by binding to it.[10]
References
- ^ "Oskar's structure revealed - Press Release - EMBL". www.embl.de.
- ^ Blondel L, Jones ET, Extavour GC (Feb 2020). "Bacterial contribution to genesis of the novel germ line determinant oskar". eLife. 24 (9): e45539. doi:10.7554/eLife.45539. PMC 7250577. PMID 32091394.
- ^ Blondel L, Besse S, Rivard EL, Ylla G, Extavour CG (Sep 2021). "Evolution of a cytoplasmic determinant: evidence for the biochemical basis of functional evolution of the novel germ line regulator oskar". Mol Biol Evol. msab284 (12): 5491–5513. doi:10.1093/molbev/msab284. PMC 8662646. PMID 34550378.
- ^ Kim-Ha J, Kerr K, Macdonald PM (May 1995). "Translational regulation of oskar mRNA by bruno, an ovarian RNA-binding protein, is essential". Cell. 81 (3): 403–12. doi:10.1016/0092-8674(95)90393-3. PMID 7736592.
- ^ Wilhelm JE, Hilton M, Amos Q, Henzel WJ (December 2003). "Cup is an eIF4E binding protein required for both the translational repression of oskar and the recruitment of Barentsz". The Journal of Cell Biology. 163 (6): 1197–204. doi:10.1083/jcb.200309088. PMC 2173729. PMID 14691132.
- ^ Chekulaeva M, Hentze MW, Ephrussi A (February 2006). "Bruno acts as a dual repressor of oskar translation, promoting mRNA oligomerization and formation of silencing particles". Cell. 124 (3): 521–33. doi:10.1016/j.cell.2006.01.031. PMID 16469699.
- ^ Jambor H, Mueller S, Bullock SL, Ephrussi A (April 2014). "A stem-loop structure directs oskar mRNA to microtubule minus ends". RNA. 20 (4): 429–39. doi:10.1261/rna.041566.113. PMC 3964905. PMID 24572808.
- ^ a b c Kistler KE, Trcek T, Hurd TR, Chen R, Liang FX, Sall J, et al. (September 2018). "Drosophila primordial germ cells". eLife. 7. doi:10.7554/eLife.37949. PMC 6191285. PMID 30260314.
- ^ Wang JT, Seydoux G (July 2014). "P granules". Current Biology. 24 (14): R637–R638. Bibcode:2014CBio...24.R637W. doi:10.1016/j.cub.2014.06.018. PMC 4966529. PMID 25050955.
- ^ Jeske M, Bordi M, Glatt S, Müller S, Rybin V, Müller CW, et al. (July 2015). "The Crystal Structure of the Drosophila Germline Inducer Oskar Identifies Two Domains with Distinct Vasa Helicase- and RNA-Binding Activities". Cell Reports. 12 (4): 587–98. doi:10.1016/j.celrep.2015.06.055. PMID 26190108.