Abstract
Messenger RNA (mRNA) localization is a powerful and prevalent mechanism of post-transcriptional gene regulation, enabling the cell to produce protein at the exact location at which it is needed. The phenomenon of mRNA localization has been observed in many types of cells in organisms ranging from yeast to man. Thus, the process appears to be widespread and highly conserved. Several model systems have been used to understand the mechanism by which mRNAs are localized. One such model, and the focus of this chapter, is the egg chamber of the female Drosophila melanogaster. The polarity of the developing Drosophila oocyte and resulting embryo relies on the specific localization of three critical mRNAs: gurken, bicoid, and oskar. If these mRNAs are not localized during oogenesis, the resulting progeny will not survive. The study of these mRNAs has served as a model for understanding the general mechanisms by which mRNAs are sorted. In this chapter, we will discuss how the localization of these mRNAs enables polarity establishment. We will also discuss the role of motor proteins in the localization pathway. Finally, we will consider potential mechanisms by which mRNAs can be anchored at their site of localization. It is likely that the lessons learned using the Drosophila oocyte model system will be applicable to mRNAs that are localized in other organisms as well.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- bcd :
-
bicoid
- dhc :
-
Dynein heavy chain
- egl :
-
Egalitarian
- grk :
-
gurken
- khc :
-
Kinesin heavy chain
- klc :
-
Kinesin light chain
- osk :
-
oskar
- RNP:
-
Ribonucleoprotein
- tm1 :
-
Tropomyosin1
References
Ables ET (2015) Drosophila oocytes as a model for understanding meiosis: an educational primer to accompany “corolla is a novel protein that contributes to the architecture of the synaptonemal complex of Drosophila”. Genetics 199:17–23
Babu K, Cai Y, Bahri S, Yang X, Chia W (2004) Roles of Bifocal, Homer, and F-actin in anchoring Oskar to the posterior cortex of Drosophila oocytes. Genes Dev 18:138–143
Bashirullah A, Cooperstock RL, Lipshitz HD (2001) Spatial and temporal control of RNA stability. Proc Natl Acad Sci USA 98:7025–7028
Berleth T, Burri M, Thoma G, Bopp D, Richstein S, Frigerio G, Noll M, Nusslein-Volhard C (1988) The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo. EMBO J 7:1749–1756
Bertrand E, Chartrand P, Schaefer M, Shenoy SM, Singer RH, Long RM (1998) Localization of ASH1 mRNA particles in living yeast. Mol Cell 2:437–445
Bilinski SM, Jaglarz MK, Tworzydlo W (2017) The pole (germ) plasm in insect oocytes. In: Kloc M (ed) Oocytes. Springer, Heidelberg
Bohl F, Kruse C, Frank A, Ferring D, Jansen RP (2000) She2p, a novel RNA-binding protein tethers ASH1 mRNA to the Myo4p myosin motor via She3p. EMBO J 19:5514–5524
Brendza KM, Rose DJ, Gilbert SP, Saxton WM (1999) Lethal kinesin mutations reveal amino acids important for ATPase activation and structural coupling. J Biol Chem 274:31506–31514
Brendza RP, Serbus LR, Duffy JB, Saxton WM (2000) A function for kinesin I in the posterior transport of oskar mRNA and Staufen protein. Science 289:2120–2122
Brendza RP, Serbus LR, Saxton WM, Duffy JB (2002) Posterior localization of dynein and dorsal-ventral axis formation depend on kinesin in Drosophila oocytes. Curr Biol 12:1541–1545
Burkhardt JK, Echeverri CJ, Nilsson T, Vallee RB (1997) Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution. J Cell Biol 139:469–484
Buxbaum AR, Haimovich G, Singer RH (2015) In the right place at the right time: visualizing and understanding mRNA localization. Nat Rev Mol Cell Biol 16:95–109
Caceres L, Nilson LA (2005) Production of gurken in the nurse cells is sufficient for axis determination in the Drosophila oocyte. Development 132:2345–2353
Cajigas IJ, Tushev G, Will TJ, tom Dieck S, Fuerst N, Schuman EM (2012) The local transcriptome in the synaptic neuropil revealed by deep sequencing and high-resolution imaging. Neuron 74:453–466
Cha BJ, Koppetsch BS, Theurkauf WE (2001) In vivo analysis of Drosophila bicoid mRNA localization reveals a novel microtubule-dependent axis specification pathway. Cell 106:35–46
Clark I, Giniger E, Ruohola-Baker H, Jan LY, Jan YN (1994) Transient posterior localization of a kinesin fusion protein reflects anteroposterior polarity of the Drosophila oocyte. Curr Biol 4:289–300
Clark IE, Jan LY, Jan YN (1997) Reciprocal localization of Nod and kinesin fusion proteins indicates microtubule polarity in the Drosophila oocyte, epithelium, neuron and muscle. Development 124:461–470
Clark A, Meignin C, Davis I (2007) A Dynein-dependent shortcut rapidly delivers axis determination transcripts into the Drosophila oocyte. Development 134:1955–1965
Dahlgaard K, Raposo AA, Niccoli T, St Johnston D (2007) Capu and Spire assemble a cytoplasmic actin mesh that maintains microtubule organization in the Drosophila oocyte. Dev Cell 13:539–553
Delanoue R, Herpers B, Soetaert J, Davis I, Rabouille C (2007) Drosophila Squid/hnRNP helps Dynein switch from a gurken mRNA transport motor to an ultrastructural static anchor in sponge bodies. Dev Cell 13:523–538
Dienstbier M, Boehl F, Li X, Bullock SL (2009) Egalitarian is a selective RNA-binding protein linking mRNA localization signals to the dynein motor. Genes Dev 23:1546–1558
Duncan JE, Warrior R (2002) The cytoplasmic dynein and kinesin motors have interdependent roles in patterning the Drosophila oocyte. Curr Biol 12:1982–1991
Ephrussi A, Lehmann R (1992) Induction of germ cell formation by oskar. Nature 358:387–392
Ephrussi A, Dickinson LK, Lehmann R (1991) Oskar organizes the germ plasm and directs localization of the posterior determinant nanos. Cell 66:37–50
Erdelyi M, Michon AM, Guichet A, Glotzer JB, Ephrussi A (1995) Requirement for Drosophila cytoplasmic tropomyosin in oskar mRNA localization. Nature 377:524–527
Forrest KM, Gavis ER (2003) Live imaging of endogenous RNA reveals a diffusion and entrapment mechanism for nanos mRNA localization in Drosophila. Curr Biol 13:1159–1168
Galjart N (2010) Plus-end-tracking proteins and their interactions at microtubule ends. Curr Biol 20:R528–R537
Gaspar I, Sysoev V, Komissarov A, Ephrussi A (2016) An RNA-binding atypical tropomyosin recruits kinesin-1 dynamically to oskar mRNPs. EMBO J 36(3):319–333
Gavis ER, Lehmann R (1992) Localization of nanos RNA controls embryonic polarity. Cell 71:301–313
Giorgi C, Yeo GW, Stone ME, Katz DB, Burge C, Turrigiano G, Moore MJ (2007) The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression. Cell 130:179–191
Glotzer JB, Saffrich R, Glotzer M, Ephrussi A (1997) Cytoplasmic flows localize injected oskar RNA in Drosophila oocytes. Curr Biol 7:326–337
Gonsalvez GB, Urbinati CR, Long RM (2005) RNA localization in yeast: moving towards a mechanism. Biol Cell 97:75–86
Gonzalez-Reyes A, Elliott H, St Johnston D (1995) Polarization of both major body axes in Drosophila by gurken-torpedo signalling. Nature 375:654–658
Gunning PW, Hardeman EC, Lappalainen P, Mulvihill DP (2015) Tropomyosin - master regulator of actin filament function in the cytoskeleton. J Cell Sci 128:2965–2974
Heraud-Farlow JE, Kiebler MA (2014) The multifunctional Staufen proteins: conserved roles from neurogenesis to synaptic plasticity. Trends Neurosci 37:470–479
Hirokawa N, Noda Y, Tanaka Y, Niwa S (2009) Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol 10:682–696
Jambor H, Mueller S, Bullock SL, Ephrussi A (2014) A stem-loop structure directs oskar mRNA to microtubule minus ends. RNA 20:429–439
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. doi:10.7554/eLife.05003
Jankovics F, Sinka R, Lukacsovich T, Erdelyi M (2002) MOESIN crosslinks actin and cell membrane in Drosophila oocytes and is required for OSKAR anchoring. Curr Biol 12:2060–2065
Januschke J, Gervais L, Dass S, Kaltschmidt JA, Lopez-Schier H, St Johnston D, Brand AH, Roth S, Guichet A (2002) Polar transport in the Drosophila oocyte requires Dynein and Kinesin I cooperation. Curr Biol 12:1971–1981
Jeske M, Bordi M, Glatt S, Muller S, Rybin V, Muller CW, Ephrussi A (2015) The crystal structure of the Drosophila germline inducer oskar identifies two Domains with distinct Vasa helicase- and RNA-binding activities. Cell Rep 12:587–598
Jolly AL, Gelfand VI (2010) Cytoplasmic microtubule sliding: an unconventional function of conventional kinesin. Commun Integr Biol 3:589–591
Jolly AL, Gelfand VI (2011) Bidirectional intracellular transport: utility and mechanism. Biochem Soc Trans 39:1126–1130
Jolly AL, Kim H, Srinivasan D, Lakonishok M, Larson AG, Gelfand VI (2010) Kinesin-1 heavy chain mediates microtubule sliding to drive changes in cell shape. Proc Natl Acad Sci USA 107:12151–12156
Kapitein LC, Hoogenraad CC (2015) Building the neuronal microtubule cytoskeleton. Neuron 87:492–506
Kardon JR, Vale RD (2009) Regulators of the cytoplasmic dynein motor. Nat Rev Mol Cell Biol 10:854–865
Kim-Ha J, Smith JL, Macdonald PM (1991) oskar mRNA is localized to the posterior pole of the Drosophila oocyte. Cell 66:23–35
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
Kloc M, Zearfoss NR, Etkin LD (2002) Mechanisms of subcellular mRNA localization. Cell 108:533–544
Krauss J, Lopez de Quinto S, Nusslein-Volhard C, Ephrussi A (2009) Myosin-V regulates oskar mRNA localization in the Drosophila oocyte. Curr Biol 19:1058–1063
Kural C, Kim H, Syed S, Goshima G, Gelfand VI, Selvin PR (2005) Kinesin and dynein move a peroxisome in vivo: a tug-of-war or coordinated movement? Science 308:1469–1472
Lawrence JB, Singer RH (1986) Intracellular localization of messenger RNAs for cytoskeletal proteins. Cell 45:407–415
Lecuyer E, Yoshida H, Parthasarathy N, Alm C, Babak T, Cerovina T, Hughes TR, Tomancak P, Krause HM (2007) Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell 131:174–187
Liu G, Sanghavi P, Bollinger KE, Perry L, Marshall B, Roon P, Tanaka T, Nakamura A, Gonsalvez GB (2015) Efficient endocytic uptake and maturation in Drosophila oocytes requires Dynamitin/p50. Genetics 201:631–649
Loiseau P, Davies T, Williams LS, Mishima M, Palacios IM (2010) Drosophila PAT1 is required for Kinesin-1 to transport cargo and to maximize its motility. Development 137:2763–2772
Long RM, Singer RH, Meng X, Gonzalez I, Nasmyth K, Jansen RP (1997) Mating type switching in yeast controlled by asymmetric localization of ASH1 mRNA. Science 277:383–387
Long RM, Gu W, Lorimer E, Singer RH, Chartrand P (2000) She2p is a novel RNA-binding protein that recruits the Myo4p-She3p complex to ASH1 mRNA. EMBO J 19:6592–6601
Lu W, Winding M, Lakonishok M, Wildonger J, Gelfand VI (2016) Microtubule-microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes. Proc Natl Acad Sci USA 113:E4995–E5004
Luders J, Stearns T (2007) Microtubule-organizing centres: a re-evaluation. Nat Rev Mol Cell Biol 8:161–167
MacDougall N, Clark A, MacDougall E, Davis I (2003) Drosophila gurken (TGFalpha) mRNA localizes as particles that move within the oocyte in two dynein-dependent steps. Dev Cell 4:307–319
Markussen FH, Michon AM, Breitwieser W, Ephrussi A (1995) Translational control of oskar generates short OSK, the isoform that induces pole plasma assembly. Development 121:3723–3732
Martin KC, Ephrussi A (2009) mRNA localization: gene expression in the spatial dimension. Cell 136:719–730
McGrail M, Hays TS (1997) The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila. Development 124:2409–2419
Medioni C, Mowry K, Besse F (2012) Principles and roles of mRNA localization in animal development. Development 139:3263–3276
Mili S, Moissoglu K, Macara IG (2008) Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions. Nature 453:115–119
Mische S, Li M, Serr M, Hays TS (2007) Direct observation of regulated ribonucleoprotein transport across the nurse cell/oocyte boundary. Mol Biol Cell 18:2254–2263
Neuman-Silberberg FS, Schupbach T (1993) The Drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGF alpha-like protein. Cell 75:165–174
Neuman-Silberberg FS, Schupbach T (1996) The Drosophila TGF-alpha-like protein Gurken: expression and cellular localization during Drosophila oogenesis. Mech Dev 59:105–113
Oh D, Houston DW (2017) RNA localization in the vertebrate oocyte: establishment of oocyte polarity and localized mRNA assemblages. In: Kloc M (ed) Oocytes. Springer, Heidelberg
Palacios IM, St Johnston D (2002) Kinesin light chain-independent function of the Kinesin heavy chain in cytoplasmic streaming and posterior localisation in the Drosophila oocyte. Development 129:5473–5485
Parton RM, Hamilton RS, Ball G, Yang L, Cullen CF, Lu W, Ohkura H, Davis I (2011) A PAR-1-dependent orientation gradient of dynamic microtubules directs posterior cargo transport in the Drosophila oocyte. J Cell Biol 194:121–135
Polesello C, Delon I, Valenti P, Ferrer P, Payre F (2002) Dmoesin controls actin-based cell shape and polarity during Drosophila melanogaster oogenesis. Nat Cell Biol 4:782–789
Presley JF, Cole NB, Schroer TA, Hirschberg K, Zaal KJ, Lippincott-Schwartz J (1997) ER-to-Golgi transport visualized in living cells. Nature 389:81–85
Quinlan ME (2016) Cytoplasmic streaming in the Drosophila oocyte. Annu Rev Cell Dev Biol 32:173–195
Quinlan ME, Hilgert S, Bedrossian A, Mullins RD, Kerkhoff E (2007) Regulatory interactions between two actin nucleators, Spire and Cappuccino. J Cell Biol 179:117–128
Rom I, Faicevici A, Almog O, Neuman-Silberberg FS (2007) Drosophila Dynein light chain (DDLC1) binds to gurken mRNA and is required for its localization. Biochim Biophys Acta 1773:1526–1533
Roth S, Neuman-Silberberg FS, Barcelo G, Schupbach T (1995) cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila. Cell 81:967–978
Sanghavi P, Lu S, Gonsalvez GB (2012) A functional link between localized Oskar, dynamic microtubules, and endocytosis. Dev Biol 367:66–77
Sanghavi P, Laxani S, Li X, Bullock SL, Gonsalvez GB (2013) Dynein associates with oskar mRNPs and is required for their efficient net plus-end localization in Drosophila oocytes. PLoS One 8:e80605
Sanghavi P, Liu G, Veeranan-Karmegam R, Navarro C, Gonsalvez GB (2016) Multiple roles for Egalitarian in polarization of the Drosophila egg chamber. Genetics 203(1):415–432
Saunders C, Cohen RS (1999) The role of oocyte transcription, the 5′UTR, and translation repression and derepression in Drosophila gurken mRNA and protein localization. Mol Cell 3:43–54
Schnorrer F, Luschnig S, Koch I, Nusslein-Volhard C (2002) Gamma-tubulin37C and gamma-tubulin ring complex protein 75 are essential for bicoid RNA localization during drosophila oogenesis. Dev Cell 3:685–696
Serbus LR, Cha BJ, Theurkauf WE, Saxton WM (2005) Dynein and the actin cytoskeleton control kinesin-driven cytoplasmic streaming in Drosophila oocytes. Development 132:3743–3752
Sil A, Herskowitz I (1996) Identification of asymmetrically localized determinant, Ash1p, required for lineage-specific transcription of the yeast HO gene. Cell 84:711–722
Singer-Kruger B, Jansen RP (2014) Here, there, everywhere. mRNA localization in budding yeast. RNA Biol 11:1031–1039
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
Spradling AC (1993) Developmental genetics of oogenesis. In: Michael Bate AMA (ed) The development of Drosophila melanogaster. Cold Spring Harbor Laboratory Press, New York
Spradling A, Drummond-Barbosa D, Kai T (2001) Stem cells find their niche. Nature 414:98–104
Steinhauer J, Kalderon D (2006) Microtubule polarity and axis formation in the Drosophila oocyte. Dev Dyn 235:1455–1468
Swan A, Nguyen T, Suter B (1999) Drosophila Lissencephaly-1 functions with Bic-D and dynein in oocyte determination and nuclear positioning. Nat Cell Biol 1:444–449
Takizawa PA, Vale RD (2000) The myosin motor, Myo4p, binds Ash1 mRNA via the adapter protein, She3p. Proc Natl Acad Sci USA 97:5273–5278
Takizawa PA, Sil A, Swedlow JR, Herskowitz I, Vale RD (1997) Actin-dependent localization of an RNA encoding a cell-fate determinant in yeast. Nature 389:90–93
Tanaka T, Nakamura A (2008) The endocytic pathway acts downstream of Oskar in Drosophila germ plasm assembly. Development 135:1107–1117
Theurkauf WE (1994) Microtubules and cytoplasm organization during Drosophila oogenesis. Dev Biol 165:352–360
Theurkauf WE, Hazelrigg TI (1998) In vivo analyses of cytoplasmic transport and cytoskeletal organization during Drosophila oogenesis: characterization of a multi-step anterior localization pathway. Development 125:3655–3666
Trovisco V, Belaya K, Nashchekin D, Irion U, Sirinakis G, Butler R, Lee JJ, Gavis ER, St Johnston D (2016) bicoid mRNA localises to the Drosophila oocyte anterior by random Dynein-mediated transport and anchoring. elife 5:e17537
Vanzo NF, Ephrussi A (2002) Oskar anchoring restricts pole plasm formation to the posterior of the Drosophila oocyte. Development 129:3705–3714
Vanzo N, Oprins A, Xanthakis D, Ephrussi A, Rabouille C (2007) Stimulation of endocytosis and actin dynamics by Oskar polarizes the Drosophila oocyte. Dev Cell 12:543–555
Veeranan-Karmegam R, Boggupalli DP, Liu G, Gonsalvez GB (2016) A new isoform of Drosophila non-muscle Tropomyosin 1 interacts with Kinesin-1 and functions in oskar mRNA localization. J Cell Sci 129:4252–4264
Weil TT, Forrest KM, Gavis ER (2006) Localization of bicoid mRNA in late oocytes is maintained by continual active transport. Dev Cell 11:251–262
Wilk R, Hu J, Blotsky D, Krause HM (2016) Diverse and pervasive subcellular distributions for both coding and long noncoding RNAs. Genes Dev 30:594–609
Zaessinger S, Busseau I, Simonelig M (2006) Oskar allows nanos mRNA translation in Drosophila embryos by preventing its deadenylation by Smaug/CCR4. Development 133:4573–4583
Zimyanin VL, Belaya K, Pecreaux J, Gilchrist MJ, Clark A, Davis I, St Johnston D (2008) In vivo imaging of oskar mRNA transport reveals the mechanism of posterior localization. Cell 134:843–853
Acknowledgments
Thanks to members of the Gonsalvez lab for critical reading and input on this manuscript. Projects on mRNA localization and microtubule motors in the Gonsalvez lab are supported by a grant from the National Institutes of Health (R01GM100088).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Goldman, C.H., Gonsalvez, G.B. (2017). The Role of Microtubule Motors in mRNA Localization and Patterning Within the Drosophila Oocyte. In: Kloc, M. (eds) Oocytes. Results and Problems in Cell Differentiation, vol 63. Springer, Cham. https://doi.org/10.1007/978-3-319-60855-6_7
Download citation
DOI: https://doi.org/10.1007/978-3-319-60855-6_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-60854-9
Online ISBN: 978-3-319-60855-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)