Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation

English version

Autoři: Annabelle Dold ^aff001; Hong Han ^aff002; Niankun Liu ^aff002; Andrea Hildebrandt ^aff003; Mirko Brüggemann ^aff005; Cornelia Rücklé ^aff005; Heike Hänel ^aff004; Anke Busch ^aff006; Petra Beli ^aff003; Kathi Zarnack ^aff005; Julian König ^aff004; Jean-Yves Roignant ^aff001; Paul Lasko ^aff002
Působiště autorů: RNA Epigenetics, Institute of Molecular Biology, Mainz, Germany ^aff001; Department of Biology, McGill University, Montréal, Québec, Canada ^aff002; Chromatin Biology and Epigenetics, Institute of Molecular Biology, Mainz, Germany ^aff003; Genomic Views of Splicing Regulation, Institute of Molecular Biology, Mainz, Germany ^aff004; Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany ^aff005; Bioinformatics Core Facility, Institute of Molecular Biology, Mainz, Germany ^aff006; Center for Integrative Genomics, Génopode Building, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland ^aff007; Department of Human Genetics, Radboud University Medical Center, GA Nijmegen, Netherlands ^aff008
Vyšlo v časopise: Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation. PLoS Genet 16(1): e32767. doi:10.1371/journal.pgen.1008581
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008581

Souhrn

Makorins are evolutionary conserved proteins that contain C₃H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila, maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar (osk). We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds specifically to osk 3’ UTR in a region adjacent to A-rich sequences. Using Drosophila S2R+ cultured cells we show that this binding site overlaps with a Bruno1 (Bru1) responsive element (BREs) that regulates osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation, most likely by competing with Bru1 to bind to osk 3’ UTR.

Klíčová slova:

3' UTR – Drosophila melanogaster – Embryos – Messenger RNA – Oocytes – Ovaries – Protein translation – Sequence motif analysis

Zdroje

1. Lasko P. 2012. mRNA localization and translational control in Drosophila oogenesis. Cold Spring Harb Perspec Biol 4(10): a012294.

2. Jambor H, Surendranath V, Kalinka AT, Mejstrik P, Saalfeld S, Tomancak P. 2015. Systematic imaging reveals features and changing localization of mRNAs in Drosophila development. eLife 4: e05003.

3. Lécuyer E, Yoshida H, Parthasarathy N, Alm C, Babak T, Cerovina T, et al. 2007. Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell 131: 174–187. doi: 10.1016/j.cell.2007.08.003 17923096

4. Zimyanin VL, Belaya K, Pecreaux J, Gilchrist MJ, Clark A, Davis I, et al. 2008. In vivo imaging of oskar mRNA transport reveals the mechanism of posterior localization. Cell 134: 843–853. doi: 10.1016/j.cell.2008.06.053 18775316

5. Glotzer JB, Saffrich R, Glotzer M, Ephrussi A. 1997. Cytoplasmic flows localize injected oskar RNA in Drosophila oocytes. Curr Biol 7: 326–337. doi: 10.1016/s0960-9822(06)00156-4 9115398

6. Ephrussi A, Lehmann R. 1992. Induction of germ cell formation by oskar. Nature 358: 387–392. doi: 10.1038/358387a0 1641021

7. Smith JL, Wilson JE, Macdonald PM. 1992. Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos. Cell 70: 849–859. doi: 10.1016/0092-8674(92)90318-7 1516136

8. Chang CW, Nashchekin D, Wheatley L, Irion U, Dahlgaard K, Montague TG, et al. 2011. Anterior-posterior axis specification in Drosophila oocytes: identification of novel bicoid and oskar mRNA localization factors. Genetics 188: 883–896. doi: 10.1534/genetics.111.129312 21625003

9. Ephrussi A, Dickinson LK, Lehmann R. 1991. Oskar organizes the germ plasm and directs localization of the posterior determinant nanos. Cell 66: 37–50. doi: 10.1016/0092-8674(91)90137-n 2070417

10. Shapiro RS, Anderson KV. 2006. Drosophila Ik2, a member of the I kappa B kinase family, is required for mRNA localization during oogenesis. Development 133: 1467–1475. doi: 10.1242/dev.02318 16540511

11. Lehmann R, Nüsslein-Volhard C. 1986. Abdominal segmentation, pole cell formation, and embryonic polarity require the localized activity of oskar, a maternal gene in Drosophila. Cell 47: 141–152. doi: 10.1016/0092-8674(86)90375-2 3093084

12. Nüsslein-Volhard C, Frohnhöfer HG, Lehmann R. 1987. Determination of anteroposterior polarity in Drosophila. Science 238: 1675–1681. doi: 10.1126/science.3686007 3686007

13. Manseau L, Calley J, Phan H. 1996. Profilin is required for posterior patterning of the Drosophila oocyte. Development 122: 2109–2116. 8681792

14. Micklem DR, Adams J, Grünert S, St Johnston D. 2000. Distinct roles of two conserved Staufen domains in oskar mRNA localization and translation. EMBO J 19: 1366–1377. doi: 10.1093/emboj/19.6.1366 10716936

15. Breitwieser W, Markussen FH, Horstmann H, Ephrussi A. 1996. Oskar protein interaction with Vasa represents an essential step in polar granule assembly. Genes Dev 10: 2179–2188. doi: 10.1101/gad.10.17.2179 8804312

16. Lasko PF, Ashburner M. 1990. Posterior localization of Vasa protein correlates with, but is not sufficient for, pole cell development. Genes Dev 4: 905–921. doi: 10.1101/gad.4.6.905 2384213

17. Wang C, Lehmann R. 1991. Nanos is the localized posterior determinant in Drosophila. Cell 66: 637–647. doi: 10.1016/0092-8674(91)90110-k 1908748

18. Kim-Ha J, Kerr K, Macdonald PM. 1995. Translational regulation of oskar mRNA by Bruno, an ovarian RNA-binding protein, is essential. Cell 81: 403–412. doi: 10.1016/0092-8674(95)90393-3 7736592

19. Lehmann R. 2016. Germ plasm biogenesis—an Oskar-centric perspective. Curr Top Dev Biol 116: 679–707. doi: 10.1016/bs.ctdb.2015.11.024 26970648

20. Webster PJ, Liang L, Berg CA, Lasko P, Macdonald PM. 1997. Translational repressor Bruno plays multiple roles in development and is widely conserved. Genes Dev 11: 2510–2521. doi: 10.1101/gad.11.19.2510 9334316

21. Nakamura A, Sato K, Hanyu-Nakamura K. 2004. Drosophila Cup is an eIF4E binding protein that associates with Bruno and regulates oskar mRNA translation in oogenesis. Dev Cell 6: 69–78. doi: 10.1016/s1534-5807(03)00400-3 14723848

22. Chekulaeva M, Hentze MW, Ephrussi A. 2006. Bruno acts as a dual repressor of oskar translation, promoting mRNA oligomerization and formation of silencing particles. Cell 124: 521–533. doi: 10.1016/j.cell.2006.01.031 16469699

23. Besse F, López de Quinto S, Marchand V, Trucco A, Ephrussi A. 2009. Drosophila PTB promotes formation of high-order RNP particles and represses oskar translation. Genes Dev 23: 195–207. doi: 10.1101/gad.505709 19131435

24. Kim G, Pai C-I, Sato K, Person MD, Nakamura A, Macdonald PM. 2015. Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression. PLoS Genet 11(2): e1004992. doi: 10.1371/journal.pgen.1004992 25723530

25. Reveal B, Yan N, Snee MJ, Pai CI, Gim Y, Macdonald PM. 2010. BREs mediate both repression and activation of oskar mRNA translation and act in trans. Dev Cell 18: 496–502. doi: 10.1016/j.devcel.2009.12.021 20230756

26. Macdonald PM, Kanke M, Kenny A. 2016. Community effects in regulation of translation. eLife 5: e10965. doi: 10.7554/eLife.10965 27104756

27. Kim-Ha J, Smith JL, Macdonald PM. 1991. oskar mRNA is localized to the posterior pole of the Drosophila oocyte. Cell 66: 23–35. doi: 10.1016/0092-8674(91)90136-m 2070416

28. Munro TP, Kwon S, Schnapp BJ, St Johnston D. 2006. A repeated IMP-binding motif controls oskar mRNA translation and anchoring independently of Drosophila melanogaster IMP. J Cell Biol 172: 577–588. doi: 10.1083/jcb.200510044 16476777

29. Wilson JE, Connell JE, Macdonald PM. 1996. aubergine enhances oskar translation in the Drosophila ovary. Development 122: 1631–1639. 8625849

30. Chang JS, Tan L, Schedl P. 1999. The Drosophila CPEB homolog, orb, is required for Oskar protein expression in oocytes. Dev Biol 215: 91–106. doi: 10.1006/dbio.1999.9444 10525352

31. Tomancak P, Berman BP, Beaton A, Weiszmann R, Kwan E, Hartenstein V, et al. 2007. Global analysis of patterns of gene expression during Drosophila embryogenesis. Genome Biol. 8: R145. doi: 10.1186/gb-2007-8-7-r145 17645804

32. Liu N, Lasko P. 2015. Analysis of RNA interference lines identifies new functions of maternally-expressed genes involved in embryonic patterning in Drosophila melanogaster. G3 (Bethesda) 5: 1025–1034.

33. Bohne A, Darras A, D'Cotta H, Baroiller JF, Galiana-Arnoux D, Volff JN. 2010. The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene. BMC Genomics 11: 721. doi: 10.1186/1471-2164-11-721 21172006

34. Kim JH, Park SM, Kang MR, Oh SY, Lee TH, Muller MT, et al. 2005. Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT. Genes Dev 19: 776–781. doi: 10.1101/gad.1289405 15805468

35. Lee EW, Lee MS, Camus S, Ghim J, Yang MR, Oh W, et al. 2009. Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell cycle arrest and apoptosis. EMBO J 28: 2100–2113. doi: 10.1038/emboj.2009.164 19536131

36. Lee MS, Han HJ, Han SY, Kim IY, Chae S, Lee CS, et al. 2018. Loss of the E3 ubiquitin ligase MKRN1 represses diet-induced metabolic syndrome through AMPK activation. Nat Commun 9: 3404 doi: 10.1038/s41467-018-05721-4 30143610

37. Cassar PA, Carpenedo RL, Samavarchi-Tehrani P, Olsen JB, Park CJ, Chang WY, et al. 2015. Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network. EMBO Rep 10: 1334–1357.

38. Carpenedo RL, Cassar PA, Stanford WL. 2016. MKRN1: Uncovering function by an unbiased systems approach. Cell Cycle 15: 303–304. doi: 10.1080/15384101.2015.1124698 26651844

39. Miroci H, Schob C, Kindler S, Olschlager-Schutt J, Fehr S, Jungenitz T, et al. 2012. Makorin ring zinc finger protein 1 (MKRN1), a novel poly(A)-binding protein-interacting protein, stimulates translation in nerve cells. J Biol Chem 287: 1322–1334. doi: 10.1074/jbc.M111.315291 22128154

40. Vazquez-Pianzola P, Urlaub H, Suter B. 2011. pAbp binds to the osk 3'UTR and specifically contributes to osk mRNA stability and oocyte accumulation. Dev Biol 357: 404–418. doi: 10.1016/j.ydbio.2011.07.009 21782810

41. Winslow GM, Carroll SB, Scott MP. 1988. Maternal-effect genes that alter the fate map of the Drosophila blastoderm embryo. Dev Biol 129: 72–83. doi: 10.1016/0012-1606(88)90162-5 3410162

42. Rongo C, Gavis ER, Lehmann R. 1995. Localization of oskar RNA regulates oskar translation and requires Oskar protein. Development 121: 2737–2746. 7555702

43. Nakamura A, Amikura R, Hanyu K, Kobayashi S. 2001. Me31B silences translation of oocyte-localizing RNAs through the formation of cytoplasmic RNP complex during Drosophila oogenesis. Development 128: 3233–3242. 11546740

44. Norvell A, Debec A, Finch D, Gibson L, Thoma B. 2005. Squid is required for efficient posterior localization of oskar mRNA during Drosophila oogenesis. Dev Genes Evol 215: 340–349. doi: 10.1007/s00427-005-0480-2 15791421

45. Steinhauer J, Kalderon D. 2005. The RNA-binding protein Squid is required for the establishment of anteroposterior polarity in the Drosophila oocyte. Development 132: 5515–5525. doi: 10.1242/dev.02159 16291786

46. Geng C, Macdonald PM. 2006. Imp associates with Squid and Hrp48 and contributes to localized expression of Gurken in the oocyte. Mol Cell Biol 26: 9508–9516. doi: 10.1128/MCB.01136-06 17030623

47. Clouse KN, Ferguson SB, Schüpbach T. 2008. Squid, Cup, and PABP55B function together to regulate gurken translation in Drosophila. Dev Biol 313: 713–724. doi: 10.1016/j.ydbio.2007.11.008 18082158

48. McDermott SM, Meignin C, Rappsilber J, Davis I. 2012. Drosophila Syncrip binds the gurken mRNA localisation signal and regulates localised transcripts during axis specification. Biol Open 1: 488–497. doi: 10.1242/bio.2012885 23213441

49. Hildebrandt A, Brüggemann M, Rücklé C, Boerner S, Heidelberger JB, Busch A, et al. 2019. The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation. Genome Biol 20: 216 doi: 10.1186/s13059-019-1814-0 31640799

50. Lee FCY and Ule J. 2018. Advances in CLIP Technologies for Studies of Protein-RNA Interactions. Mol Cell 69:354–369 doi: 10.1016/j.molcel.2018.01.005 29395060

51. Jenny A, Hachet O, Závorszky P, Cyrklaff A, Weston MDJ, St Johnston D, et al. 2006. A translation-independent role of oskar RNA in early Drosophila oogenesis. Development 133: 2827–2833. doi: 10.1242/dev.02456 16835436

52. Schüpbach T, Wieschaus E. 1991. Female sterile mutations on the second chromosome of Drosophila melanogaster. Genetics 129: 1119–1136. 1783295

53. Jeong EB, Jeong SS, Cho E, Kim EY. 2019. Makorin 1 is required for Drosophila oogenesis by regulating insulin/Tor signaling. PLoS ONE 14(4): e0215688. doi: 10.1371/journal.pone.0215688 31009498

54. Castagnetti S, Ephrussi A. 2003. Orb and a long poly(A) tail are required for efficient oskar translation at the posterior pole of the Drosophila oocyte. Development 130: 835–843. doi: 10.1242/dev.00309 12538512

55. Ryu YH, Macdonald PM. 2015. RNA sequences required for the noncoding function of oskar RNA also mediate regulation of Oskar protein expression by Bicoid Stability Factor. Dev Biol 407: 211–223. doi: 10.1016/j.ydbio.2015.09.014 26433064

56. Filardo P, Ephrussi A. 2003. Bruno regulates gurken during Drosophila oogenesis. Mech Dev 120: 289–297. doi: 10.1016/s0925-4773(02)00454-9 12591598

57. Reveal B, Garcia C, Ellington A, Macdonald PM. 2011. Multiple RNA binding domains of Bruno confer recognition of diverse binding sites for translational repression. RNA Biol 8: 1047–1060. doi: 10.4161/rna.8.6.17542 21955496

58. Qian X, Wang L, Zheng B, Shi ZM, Ge X, Jiang CF, et al. 2016. Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility. Sci Rep 6: 39318. doi: 10.1038/srep39318 28008940

59. Lécuyer E, Parthasarathy N, Krause HM. 2008. Fluorescent in situ hybridization protocols in Drosophila embryos and tissues. Methods Mol Biol 420: 289–302. doi: 10.1007/978-1-59745-583-1_18 18641955

60. Lence T, Akhtar J, Bayer M, Schmid K, Spindler L, Ho CH, et al. 2016. m6A modulates neuronal functions and sex determination in Drosophila. Nature 540: 242–247. doi: 10.1038/nature20568 27919077

61. Na H, Laver JD, Jeon J, Singh F, Ancevicius K, Fan Y, et al. 2016. A high-throughput pipeline for the production of synthetic antibodies for analysis of ribonucleoprotein complexes. RNA 22: 636–655. doi: 10.1261/rna.055186.115 26847261

62. Hildebrandt A, Alanis-Lobato G, Voigt A, Zarnack K, Andrade-Navarro MA, Beli P, et al. J. 2017. Interaction profiling of RNA-binding ubiquitin ligases reveals a link between posttranscriptional regulation and the ubiquitin system. Sci Rep 7: 16582. doi: 10.1038/s41598-017-16695-6 29185492

63. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. 2015 limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43: e47. doi: 10.1093/nar/gkv007 25605792

64. Wickham H. 2016. ggplot2: Elegant Graphics for Data Analysis. Springer-Verlag New York.

65. Ebersberger I, Simm S, Leisegang MS, Schmitzberger P, Mirus O, von Haeseler A, et al. 2014. The evolution of the ribosome biogenesis pathway from a yeast perspective. Nucleic Acids Res 42: 1509–1523. doi: 10.1093/nar/gkt1137 24234440

66. Sonnhammer EL, Gabaldón T, Sousa da Silva AW, Martin M, Robinson-Rechavi M, Boeckmann B, et al. 2014. Big data and other challenges in the quest for orthologs. Bioinformatics 30: 2993–2998. doi: 10.1093/bioinformatics/btu492 25064571

67. Koestler T, von Haeseler A, Ebersberger I. 2010. FACT: functional annotation transfer between proteins with similar feature architectures. BMC Bioinformatics 11: 417. doi: 10.1186/1471-2105-11-417 20696036

68. Katoh K, Standley DM. 2013. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30: 772–780. doi: 10.1093/molbev/mst010 23329690

69. Sutandy FX, Hildebrandt A, König J. 2016. Profiling the binding sites of RNA-binding proteins with nucleotide resolution using iCLIP. Methods Mol Biol 1358: 175–195. doi: 10.1007/978-1-4939-3067-8_11 26463384

70. Dodt M, Roehr JT, Ahmed R, and Dieterich C. 2012. Flexbar–flexible barcode and adapter processing for next-generation sequencing platforms. MDPI Biology, 1(3): 895–905.

71. Aken BL, Achuthan P, Akanni W, Amode MR, Bernsdorff F, Bhai J, et al. 2017. Ensembl 2017. Nucleic Acids Res 45: D635–D642. doi: 10.1093/nar/gkw1104 27899575

72. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. 2013. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29: 15–21. doi: 10.1093/bioinformatics/bts635 23104886

73. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. 2009. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079. doi: 10.1093/bioinformatics/btp352 19505943

74. Quinlan AR, Hall IM. 2010. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26: 841–842. doi: 10.1093/bioinformatics/btq033 20110278

75. Kent WJ, Zweig AS, Barber G, Hinrichs AS, Karolchik D. 2010. BigWig and BigBed: enabling browsing of large distributed data sets. Bioinformatics 26: 2204–2207. doi: 10.1093/bioinformatics/btq351 20639541

76. Edgar R, Domrachev M, Lash AE. 2002. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207–210. doi: 10.1093/nar/30.1.207 11752295

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