Intracellular mRNA localization: motors move messages.

Intracellular mRNA localization is a common mechanism of post-transcriptional regulation of gene expression. In a wide range of organisms, mRNA localization coupled with translational regulation target the proteins to their site of function. Here, we describe recent exciting evidence that some mRNAs are transported as particles along the cytoskeleton by the molecular motors dynein, kinesin or myosin. We discuss the key questions of how localized mRNAs might be linked to motors and what determines their cytoplasmic destinations.

[1]  R. Kelley,et al.  Specific isoforms of squid, a Drosophila hnRNP, perform distinct roles in Gurken localization during oogenesis. , 1999, Genes & development.

[2]  M. Kloc,et al.  Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster , 1999, The EMBO journal.

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

[4]  S. Lall,et al.  Squid hnRNP Protein Promotes Apical Cytoplasmic Transport and Localization of Drosophila Pair-Rule Transcripts , 1999, Cell.

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

[6]  R. Steward,et al.  Lis1, the Drosophila homolog of a human lissencephaly disease gene, is required for germline cell division and oocyte differentiation. , 1999, Development.

[7]  W. Theurkauf,et al.  Kinesin I-dependent cortical exclusion restricts pole plasm to the oocyte posterior , 2002, Nature Cell Biology.

[8]  E. Raff,et al.  Kinesin heavy chain is essential for viability and neuromuscular functions in Drosophila, but mutants show no defects in mitosis , 1991, Cell.

[9]  David Ish-Horowicz,et al.  Conserved signals and machinery for RNA transport in Drosophila oogenesis and embryogenesis , 2001, Nature.

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

[11]  R. Jansen,et al.  mRNA localization: message on the move , 2001, Nature Reviews Molecular Cell Biology.

[12]  J. Carson,et al.  Transport and localization of exogenous myelin basic protein mRNA microinjected into oligodendrocytes , 1993, The Journal of cell biology.

[13]  G. Odell,et al.  Cytoarchitecture and the patterning of fushi tarazu expression in the Drosophila blastoderm. , 1987, Genes & Development.

[14]  Malgorzata Kloc,et al.  Mechanisms of Subcellular mRNA Localization , 2002, Cell.

[15]  L. Goldstein,et al.  Kinesin-Dependent Axonal Transport Is Mediated by the Sunday Driver (SYD) Protein , 2000, Cell.

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

[17]  R. Lehmann,et al.  A selective screen reveals discrete functional domains in Drosophila Nanos. , 1999, Genetics.

[18]  Ilan Davis,et al.  Drosophila wingless and Pair-Rule Transcripts Localize Apically by Dynein-Mediated Transport of RNA Particles , 2001, Cell.

[19]  J. Silver,et al.  Dynein light chain binding to a 3'-untranslated sequence mediates parathyroid hormone mRNA association with microtubules. , 2000, The Journal of clinical investigation.

[20]  H. Krause,et al.  Apical Localization of wingless Transcripts Is Required for Wingless Signaling , 2001, Cell.

[21]  W. Theurkauf,et al.  In Vivo Analysis of Drosophila bicoid mRNA Localization Reveals a Novel Microtubule-Dependent Axis Specification Pathway , 2001, Cell.

[22]  A. Kamal,et al.  Connecting vesicle transport to the cytoskeleton. , 2000, Current opinion in cell biology.

[23]  D. L. Weeks,et al.  Identification and cloning of localized maternal RNAs from xenopus eggs , 1985, Cell.

[24]  J. Derisi,et al.  Plasma membrane compartmentalization in yeast by messenger RNA transport and a septin diffusion barrier. , 2000, Science.

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

[26]  D. St Johnston,et al.  Distinct roles of two conserved Staufen domains in oskar mRNA localization and translation , 2000, The EMBO journal.

[27]  Ed Hurt,et al.  A Conserved mRNA Export Machinery Coupled to pre-mRNA Splicing , 2002, Cell.

[28]  E. Wieschaus,et al.  Dominant maternal-effect mutations of Drosophila melanogaster causing the production of double-abdomen embryos. , 1986, Genetics.

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

[30]  C. Turck,et al.  Isolation of a Ribonucleoprotein Complex Involved in mRNA Localization in Drosophila Oocytes , 2000, The Journal of cell biology.

[31]  B. Daneholt.  A Look at Messenger RNP Moving through the Nuclear Pore , 1997, Cell.

[32]  R. Singer,et al.  Localization of ASH1 mRNA particles in living yeast. , 1998, Molecular cell.

[33]  O. Cohen-Fix,et al.  Separase: a conserved protease separating more than just sisters. , 2002, Trends in cell biology.

[34]  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.

[35]  C. Smibert,et al.  Mechanisms of RNA localization and translational regulation. , 2000, Current opinion in genetics & development.

[36]  Ira Herskowitz,et al.  Identification of an Asymmetrically Localized Determinant, Ash1p, Required for Lineage-Specific Transcription of the Yeast HO Gene , 1996, Cell.

[37]  B. Suter,et al.  Drosophila Lissencephaly-1 functions with Bic-D and dynein in oocyte determination and nuclear positioning , 1999, Nature Cell Biology.

[38]  Richard Benton,et al.  The Drosophila Homolog of C. elegans PAR-1 Organizes the Oocyte Cytoskeleton and Directs oskar mRNA Localization to the Posterior Pole , 2000, Cell.

[39]  Kim Nasmyth,et al.  Asymmetric Accumulation of Ash1p in Postanaphase Nuclei Depends on a Myosin and Restricts Yeast Mating-Type Switching to Mother Cells , 1996, Cell.

[40]  W. Saxton,et al.  A function for kinesin I in the posterior transport of oskar mRNA and Staufen protein. , 2000, Science.

[41]  J. Hammer,et al.  Rabs grab motors: defining the connections between Rab GTPases and motor proteins. , 2002, Current opinion in cell biology.

[42]  R. Cohen,et al.  Rab11 polarization of the Drosophila oocyte: a novel link between membrane trafficking, microtubule organization, and oskar mRNA localization and translation. , 2002, Development.

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

[44]  I. Palacios.  RNA Processing: Splicing and the Cytoplasmic Localisation of mRNA , 2002, Current Biology.

[45]  D. St Johnston,et al.  Getting the message across: the intracellular localization of mRNAs in higher eukaryotes. , 2001, Annual review of cell and developmental biology.

[46]  James O. Deshler,et al.  A highly conserved RNA-binding protein for cytoplasmic mRNA localization in vertebrates , 1998, Current Biology.

[47]  K. Nasmyth,et al.  Mother Cell–Specific HO Expression in Budding Yeast Depends on the Unconventional Myosin Myo4p and Other Cytoplasmic Proteins , 1996, Cell.

[48]  R. Singer,et al.  Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype , 1994, The Journal of cell biology.

[49]  T. Schroer,et al.  Dynactin increases the processivity of the cytoplasmic dynein motor , 1999, Nature Cell Biology.

[50]  S. Deacon,et al.  Motor-cargo interactions: the key to transport specificity. , 2002, Trends in cell biology.

[51]  R. Singer,et al.  The nuclear connection in RNA transport and localization. , 2002, Trends in cell biology.

[52]  A. Ephrussi,et al.  Par-1 regulates stability of the posterior determinant Oskar by phosphorylation , 2002, Nature Cell Biology.

[53]  K. Nasmyth,et al.  Mating type switching in yeast controlled by asymmetric localization of ASH1 mRNA. , 1997, Science.

[54]  C. Nüsslein-Volhard,et al.  The molecular motor dynein is involved in targeting Swallow and bicoid RNA to the anterior pole of Drosophila oocytes , 2000, Nature Cell Biology.

[55]  F. V. van Eeden,et al.  Barentsz is essential for the posterior localization of oskar mRNA and colocalizes with it to the posterior pole , 2001, The Journal of cell biology.

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

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

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

[59]  R. Lehmann,et al.  Translational regulation of nanos by RNA localization , 1994, Nature.

[60]  J. Eberwine,et al.  Localization and translation of mRNA in dentrites and axons , 2001, Nature Reviews Neuroscience.

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

[62]  A. Ephrussi,et al.  Drosophila Y14 shuttles to the posterior of the oocyte and is required for oskar mRNA transport , 2001, Current Biology.

[63]  R. Singer,et al.  She2p is a novel RNA‐binding protein that recruits the Myo4p–She3p complex to ASH1 mRNA , 2000, The EMBO journal.

[64]  Stella Aronov,et al.  Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules , 2002, Journal of Cell Science.

[65]  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.

[66]  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.

[67]  P. Lasko,et al.  Translational regulation and RNA localization in Drosophila oocytes and embryos. , 2001, Annual review of genetics.

[68]  E. R. Gavis,et al.  Role for mRNA localization in translational activation but not spatial restriction of nanos RNA. , 1999, Development.

[69]  Jason R. Swedlow,et al.  Actin-dependent localization of an RNA encoding a cell-fate determinant in yeast , 1997, Nature.

[70]  H. Le Hir,et al.  The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon–exon junctions , 2000, The EMBO journal.

[71]  D. Melton,et al.  A two-step model for the localization of maternal mRNA in Xenopus oocytes: involvement of microtubules and microfilaments in the translocation and anchoring of Vg1 mRNA. , 1990, Development.

[72]  D. Johnston,et al.  Kinesin light chain-independent function of the Kinesin heavy chain in cytoplasmic streaming and posterior localisation in the Drosophila oocyte , 2002, Development.

[73]  R. Singer,et al.  β-Actin Messenger RNA Localization and Protein Synthesis Augment Cell Motility , 1997, The Journal of cell biology.

[74]  A. Brand,et al.  Polar Transport in the Drosophila Oocyte Requires Dynein and Kinesin I Cooperation , 2002, Current Biology.

[75]  C. Cote,et al.  RNA sorting in Xenopus oocytes and embryos , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[76]  H. Nishida,et al.  macho-1 encodes a localized mRNA in ascidian eggs that specifies muscle fate during embryogenesis , 2001, Nature.

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

[78]  T. Hays,et al.  A molecular genetic analysis of the interaction between the cytoplasmic dynein intermediate chain and the glued (dynactin) complex. , 2000, Molecular biology of the cell.

[79]  U. Tepass,et al.  crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia , 1990, Cell.