RNA sorting in Drosophila oocytes and embryos

Many RNAs involved in determination of the oocyte, specification of embryonic axes, and establishment of germ cells in Drosophila are localized asymmetrically within the developing egg or syncytial embryo. Here I review the current state of knowledge about the cis‐acting sequences involved in RNA targeting, RNA binding proteins; gene activities implicated in localizing specific RNAs, and the role of the tubulin and actin cytoskeletons in RNA sorting within the oocyte. Targeted RNAs are often under complex translational control, and the translational control of two RNAs that localize to the posterior of the oocyte, oskar and nanos, is also discussed. Prospects for filling gaps in our knowledge about the mechanisms of localizing RNAs and the importance of RNA sorting in regulating gene expression are also explored.—Lasko, P. RNA sorting in Drosophila oocytes and embryos. FASEB J. 13, 421–433 (1999)

[1]  J. Calley,et al.  Cappuccino, a Drosophila maternal effect gene required for polarity of the egg and embryo, is related to the vertebrate limb deformity locus. , 1995, Genes & development.

[2]  Y. Jan,et al.  Transient posterior localization of a kinesin fusion protein reflects anteroposterior polarity of the Drosophila oocyte , 1994, Current Biology.

[3]  D. Ish-Horowicz,et al.  Apical localization of pair-rule transcripts requires 3′ sequences and limits protein diffusion in the Drosophila blastoderm embryo , 1991, Cell.

[4]  P. Macdonald,et al.  aubergine enhances oskar translation in the Drosophila ovary. , 1996, Development.

[5]  M. Jacobs-Lorena,et al.  Regulation of mRNA stability in development. , 1994, Annual review of genetics.

[6]  B. Alberts,et al.  A central role for microtubules in the differentiation of Drosophila oocytes. , 1993, Development.

[7]  R. Lehmann,et al.  oskar organizes the germ plasm and directs localization of the posterior determinant nanos , 1991, Cell.

[8]  A. Ephrussi,et al.  Efficient translation and phosphorylation of Oskar require Oskar protein and the RNA helicase Vasa. , 1997, Cold Spring Harbor symposia on quantitative biology.

[9]  P. Schedl,et al.  The Drosophila orb gene is predicted to encode sex-specific germline RNA-binding proteins and has localized transcripts in ovaries and early embryos. , 1992, Development.

[10]  S. Richard,et al.  Premature Translation of oskar in Oocytes Lacking the RNA-Binding Protein Bicaudal-C , 1998, Molecular and Cellular Biology.

[11]  H. Ruohola-Baker,et al.  Expression of constitutively active Notch arrests follicle cells at a precursor stage during Drosophila oogenesis and disrupts the anterior-posterior axis of the oocyte. , 1996, Development.

[12]  R. King Ovarian Development in Drosophila Melanogaster , 1970 .

[13]  D. St Johnston,et al.  Patterning of the follicle cell epithelium along the anterior-posterior axis during Drosophila oogenesis. , 1998, Development.

[14]  A. Brand,et al.  The mago nashi gene is required for the polarisation of the oocyte and the formation of perpendicular axes in Drosophila , 1997, Current Biology.

[15]  T. Schüpbach,et al.  cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila , 1995, Cell.

[16]  A. Guichet,et al.  Oocyte polarity depends on regulation of gurken by Vasa. , 1998, Development.

[17]  P. Macdonald,et al.  Mutational Analysis of an RNA Recognition Element That Mediates Localization of bicoid mRNA , 1998, Molecular and Cellular Biology.

[18]  P. Macdonald,et al.  Redundant RNA recognition events in bicoid mRNA localization. , 1997, RNA.

[19]  J. L. Smith,et al.  RNA regulatory element BLE1 directs the early steps of bicoid mRNA localization. , 1993, Development.

[20]  S. Mohr,et al.  mago nashi mediates the posterior follicle cell-to-oocyte signal to organize axis formation in Drosophila. , 1997, Development.

[21]  L. Cooley,et al.  chickadee encodes a profilin required for intercellular cytoplasm transport during Drosophila oogenesis , 1992, Cell.

[22]  P. Macdonald,et al.  oskar mRNA is localized to the posterior pole of the Drosophila oocyte , 1991, Cell.

[23]  T. Hays,et al.  The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila. , 1997, Development.

[24]  R. Lehmann,et al.  The Pumilio protein binds RNA through a conserved domain that defines a new class of RNA-binding proteins. , 1997, RNA.

[25]  R. Lehmann,et al.  Genetics of nanos localization in Drosophila , 1994, Developmental dynamics : an official publication of the American Association of Anatomists.

[26]  L. Christerson,et al.  orb is required for anteroposterior and dorsoventral patterning during Drosophila oogenesis. , 1994, Genes & development.

[27]  R. Wharton,et al.  Binding of pumilio to maternal hunchback mRNA is required for posterior patterning in drosophila embryos , 1995, Cell.

[28]  Y. Jan,et al.  The germ cell-less gene product: A posteriorly localized component necessary for germ cell development in Drosophila , 1992, Cell.

[29]  Ruth Lehmann,et al.  Induction of germ cell formation by oskar , 1992, Nature.

[30]  R. Cohen,et al.  Gratuitous mRNA localization in the Drosophila oocyte. , 1995, Development.

[31]  P. Lasko,et al.  Requirement for a Noncoding RNA in Drosophila Polar Granules for Germ Cell Establishment , 1996, Science.

[32]  Dominique Ferrandon,et al.  Staufen protein associates with the 3′UTR of bicoid mRNA to form particles that move in a microtubule-dependent manner , 1994, Cell.

[33]  P. Lasko,et al.  vasa is required for GURKEN accumulation in the oocyte, and is involved in oocyte differentiation and germline cyst development. , 1998, Development.

[34]  R. Steward,et al.  Bicaudal-D, a Drosophila gene involved in developmental asymmetry: localized transcript accumulation in ovaries and sequence similarity to myosin heavy chain tail domains. , 1989, Genes & development.

[35]  R. Cohen,et al.  Comparative analysis of the kinetics and dynamics of K10, bicoid, and oskar mRNA localization in the Drosophila oocyte. , 1996, Developmental genetics.

[36]  R. Boswell,et al.  tudor, a posterior-group gene of Drosophila melanogaster, encodes a novel protein and an mRNA localized during mid-oogenesis. , 1991, Genes & development.

[37]  J. Dubnau,et al.  RNA recognition and translational regulation by a homeodomain protein , 1996, Nature.

[38]  T. Hazelrigg,et al.  Implications for bcd mRNA localization from spatial distribution of exu protein in Drosophila oogenesis , 1994, Nature.

[39]  K. Miller,et al.  A Class VI Unconventional Myosin Is Associated with a Homologue of a Microtubule-binding Protein, Cytoplasmic Linker Protein–170, in Neurons and at the Posterior Pole of Drosophila Embryos , 1998, The Journal of cell biology.

[40]  R. Cohen,et al.  A small predicted stem-loop structure mediates oocyte localization of Drosophila K10 mRNA. , 1995, Development.

[41]  H. Ruohola-Baker,et al.  maelstrom is required for an early step in the establishment of Drosophila oocyte polarity: posterior localization of grk mRNA. , 1997, Development.

[42]  Y. Jan,et al.  Reciprocal localization of Nod and kinesin fusion proteins indicates microtubule polarity in the Drosophila oocyte, epithelium, neuron and muscle. , 1997, Development.

[43]  A. Michon,et al.  Translational control of oskar generates short OSK, the isoform that induces pole plasma assembly. , 1995, Development.

[44]  R. Wharton,et al.  The Nanos gradient in Drosophila embryos is generated by translational regulation. , 1996, Genes & development.

[45]  P. Macdonald,et al.  exl protein specifically binds BLE1, a bicoid mRNA localization element, and is required for one phase of its activity. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Joel N. Dubowy,et al.  Localization of mRNAs to the oocyte is common in Drosophila ovaries , 1998, Mechanisms of Development.

[47]  T. Hays,et al.  Drosophila cytoplasmic dynein, a microtubule motor that is asymmetrically localized in the oocyte , 1994, The Journal of cell biology.

[48]  P. Macdonald,et al.  Translational regulation of oskar mRNA by Bruno, an ovarian RNA-binding protein, is essential , 1995, Cell.

[49]  P. Schedl,et al.  Multiple cis-acting targeting sequences are required for orb mRNA localization during Drosophila oogenesis , 1994, Molecular and cellular biology.

[50]  T. Iida,et al.  Essential role of mitochondrially encoded large rRNA for germ-line formation in Drosophila embryos. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[51]  B. Suter,et al.  Null alleles reveal novel requirements for Bic-D during Drosophila oogenesis and zygotic development. , 1994, Development.

[52]  John R. Pringle,et al.  Bni1p, a Yeast Formin Linking Cdc42p and the Actin Cytoskeleton During Polarized Morphogenesis , 1997, Science.

[53]  R. Vale,et al.  RNA on the move: the mRNA localization pathway [published erratum appears in J Cell Biol 1993 Dec;123(6 Pt 1):1625] , 1993, The Journal of cell biology.

[54]  P. Lasko,et al.  Localized Bicaudal‐C RNA encodes a protein containing a KH domain, the RNA binding motif of FMR1 , 1995, The EMBO journal.

[55]  H. Jäckle,et al.  Lack of Drosophila cytoskeletal tropomyosin affects head morphogenesis and the accumulation of oskar mRNA required for germ cell formation. , 1996, The EMBO journal.

[56]  D. Kalderon,et al.  RNA localization along the anteroposterior axis of the Drosophila oocyte requires PKA-mediated signal transduction to direct normal microtubule organization. , 1994, Genes & development.

[57]  E Westhof,et al.  RNA–RNA interaction is required for the formation of specific bicoid mRNA 3′ UTR–STAUFEN ribonucleoprotein particles , 1997, The EMBO journal.

[58]  C. Nüsslein-Volhard,et al.  Multiple steps in the localization of bicoid RNA to the anterior pole of the Drosophila oocyte. , 1989, Development.

[59]  J. Calley,et al.  Profilin is required for posterior patterning of the Drosophila oocyte. , 1996, Development.

[60]  Marek Mlodzik,et al.  Expression of the caudal gene in the germ line of Drosophila: Formation of an RNA and protein gradient during early embryogenesis , 1987, Cell.

[61]  P. Macdonald,et al.  Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos , 1992, Cell.

[62]  D. Curtis,et al.  Identification of cis-acting sequences that control nanos RNA localization. , 1996, Developmental biology.

[63]  R. Boswell,et al.  Distribution of tudor protein in the Drosophila embryo suggests separation of functions based on site of localization. , 1993, Development.

[64]  D. Glover,et al.  Discrete sequence elements control posterior pole accumulation and translational repression of maternal cyclin B RNA in Drosophila. , 1993, The EMBO journal.

[65]  P. Lasko,et al.  Localization of vasa protein to the Drosophila pole plasm is independent of its RNA-binding and helicase activities. , 1994, Development.

[66]  R. Lehmann,et al.  A conserved 90 nucleotide element mediates translational repression of nanos RNA. , 1996, Development.

[67]  Tony Berry Redundant , 1989 .

[68]  B. Edgar,et al.  Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program. , 1996, Genes & development.

[69]  H. Horstmann,et al.  Oskar protein interaction with Vasa represents an essential step in polar granule assembly. , 1996, Genes & development.

[70]  R. Lehmann,et al.  Regulated synthesis, transport and assembly of the Drosophila germ plasm. , 1996, Trends in genetics : TIG.

[71]  B. Suter,et al.  Role of Bicaudal-D in patterning the Drosophila egg chamber in mid-oogenesis. , 1996, Development.

[72]  R. Lehmann,et al.  Localization of oskar RNA regulates oskar translation and requires Oskar protein. , 1995, Development.

[73]  B. Alberts,et al.  Reorganization of the cytoskeleton during Drosophila oogenesis: implications for axis specification and intercellular transport. , 1992, Development.

[74]  A. Ephrussi,et al.  Cytoplasmic flows localize injected oskar RNA in Drosophila oocytes , 1997, Current Biology.

[75]  Peter A. Lawrence,et al.  Control of Drosophila body pattern by the hunchback morphogen gradient , 1992, Cell.

[76]  J. L. Smith,et al.  Multiple RNA regulatory elements mediate distinct steps in localization of oskar mRNA. , 1993, Development.

[77]  M. Jacobs-Lorena,et al.  Developmental Regulation of bicoid mRNA Stability Is Mediated by the First 43 Nucleotides of the 3′ Untranslated Region , 1998, Molecular and Cellular Biology.

[78]  D. St Johnston,et al.  Role of oocyte position in establishment of anterior-posterior polarity in Drosophila. , 1994, Science.

[79]  Daniel St Johnston,et al.  staufen, a gene required to localize maternal RNAs in the Drosophila egg , 1991, Cell.

[80]  D. Glover,et al.  3' non-translated sequences in Drosophila cyclin B transcripts direct posterior pole accumulation late in oogenesis and peri-nuclear association in syncytial embryos. , 1992, Development.

[81]  W. Theurkauf Premature microtubule-dependent cytoplasmic streaming in cappuccino and spire mutant oocytes. , 1994, Science.

[82]  A. Sachs,et al.  Association of the yeast poly(A) tail binding protein with translation initiation factor eIF‐4G. , 1996, The EMBO journal.

[83]  D. Ruden,et al.  A Drosophila kinesin-like protein, Klp38B, functions during meiosis, mitosis, and segmentation. , 1997, Developmental biology.

[84]  P. Lasko,et al.  Translational repressor bruno plays multiple roles in development and is widely conserved. , 1997, Genes & development.

[85]  Y. Jan,et al.  Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila , 1991, Cell.

[86]  D. Montell,et al.  Requirement for the vasa RNA helicase in gurken mRNA localization. , 1998, Developmental biology.

[87]  Y. Jan,et al.  The role of gene cassettes in axis formation during Drosophila oogenesis. , 1994, Trends in genetics : TIG.

[88]  D. Johnston,et al.  Polarization of both major body axes in Drosophila by gurken-torpedo signalling , 1995, Nature.

[89]  H. Lipshitz,et al.  Mitochondrially encoded 16S large ribosomal RNA is concentrated in the posterior polar plasm of early Drosophila embryos but is not required for pole cell formation. , 1994, Developmental biology.

[90]  A. Ephrussi,et al.  Localization-dependent translation requires a functional interaction between the 5' and 3' ends of oskar mRNA. , 1998, Genes & development.

[91]  D Bopp,et al.  The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo. , 1988, The EMBO journal.

[92]  D. Ish-Horowicz,et al.  Asymmetric localization of Drosophila pair‐rule transcripts from displaced nuclei: evidence for directional nuclear export. , 1996, The EMBO journal.

[93]  Dierk Niessing,et al.  RNA binding and translational suppression by bicoid , 1996, Nature.

[94]  S. Kobayashi,et al.  Presence of mitochondrial large ribosomal RNA outside mitochondria in germ plasm of Drosophila melanogaster. , 1993, Science.

[95]  C. Smibert,et al.  smaug protein represses translation of unlocalized nanos mRNA in the Drosophila embryo. , 1996, Genes & development.

[96]  T. Schüpbach,et al.  The drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGFα-like protein , 1993, Cell.

[97]  O. Aït-Ahmed,et al.  Implication of a 5′ coding sequence in targeting maternal mRNA to the Drosophila oocyte , 1997, Mechanisms of Development.

[98]  A. Michon,et al.  Requirement for Drosophila cytoplasmic tropomyosin in oskar mRNA localization , 1995, Nature.

[99]  R. Steward,et al.  Requirement for phosphorylation and localization of the Bicaudal-D protein in Drosophila oocyte differentiation , 1991, Cell.

[100]  C. Nüsslein-Volhard,et al.  The origin of pattern and polarity in the Drosophila embryo , 1992, Cell.

[101]  M. Ashburner,et al.  Posterior localization of vasa protein correlates with, but is not sufficient for, pole cell development. , 1990, Genes & development.

[102]  T. Hazelrigg,et al.  In vivo analyses of cytoplasmic transport and cytoskeletal organization during Drosophila oogenesis: characterization of a multi-step anterior localization pathway. , 1998, Development.

[103]  R. Lehmann,et al.  An Egalitarian-BicaudalD complex is essential for oocyte specification and axis determination in Drosophila. , 1997, Genes & development.

[104]  L. Paillard,et al.  EDEN and EDEN‐BP, a cis element and an associated factor that mediate sequence‐specific mRNA deadenylation in Xenopus embryos , 1998, The EMBO journal.

[105]  E C Stephenson,et al.  Microtubules mediate the localization of bicoid RNA during Drosophila oogenesis. , 1991, Development.

[106]  R. Wharton,et al.  The Pumilio RNA-binding domain is also a translational regulator. , 1998, Molecular cell.

[107]  Y. Jan,et al.  Identification of a component of Drosophila polar granules. , 1988, Development.