Department of Zoology

Principal Investigators

Research area - Developmental Biology

Function of motor proteins and the mechanism of mRNA localisation during development

Research in the lab is directed towards understanding the mechanisms involved in the early development of an organism, including RNA processing and how asymmetries are generated at the single cell level. More specifically, we have been studying the function of the motor protein Kinesin in establishing these asymmetries, and the mechanism by which localised mRNAs are distributed within the cell. We are employing biochemical, cell biological and genetic approaches to study these processes in the fruitfly Drosophila melanogaster.

Molecular motor proteins such as Kinesin are responsible for many of the major microtubule-dependent transport pathways in neuronal and non-neuronal cells. Elucidating these pathways is an area of increasing importance and intense investigation, with possible implications in human diseases, such as neurodegeneration. We are using the Drosophila oocyte as a model system to study the nature of the cargoes moved by Kinesin, to identify the proteins that link kinesin to these cargoes and to analyse how the activity of Kinesin is modulated by these interactions.

One of the cargoes of Kinesin is oskar mRNA. The localisation of oskar mRNA in the oocyte is essential to define the anterior-posterior axis of the embryo. How the localization of determinants that establish the body axes is achieved has interested developmental biologists for many years. Since it was found out that one way to localise the determinant is to localise the transcripts that encode them, it became clear that some aspects of mRNA processing, such as localisation, play an essential role in the determination of the cell polarity and body asymmetries. We are studying the Kinesin-dependent localisation of oskar mRNA in the oocyte as a model system to understand how RNAs are asymmetrically distributed to specific regions in the cell.

To further understand how mRNAs localise, we are also studying the proteins that directly interact with the transcript and form the localisation complex. These proteins include components of the exon-exon junction complex which are loaded onto osk mRNA inside the nucleus in a splicing-dependent manner. We are interested in characterising the molecular function of this complex. For example, it is not yet known which, if any, of these proteins mediate the interaction between oskar mRNA and Kinesin, or give rise to the localisation specificity. In collaboration with Dr. E. Izaurralde and co-workers, we have shown that this protein complex is conserved in mammals, where it functions in non-sense-mediated mRNA decay (NMD), a surveillance mechanism that essential for proper gene expression as well as the degradation of aberrant mRNAs. The NMD pathway has a direct impact on hundreds of genetic disorders; about a quarter of all known mutations are predicted to trigger NMD. We are interested in analysing further what is the relation of these two post-transcriptional events: mRNA localization and mRNA surveillance.

Research group - Palacios Lab

Selected publications

• Avery P, Vicente-Crespo M, Francis D, Nashchekina O, Alonso CR, and Palacios IM (2011) “Drosophila Upf1 and Upf2 loss of function inhibits cell growth and causes animal death in a Upf3-independent manner”. RNA 17: 624-638. Described as “of outstanding interest” by Hwang, J and Maquat, LE, Curr. Opin. Genet Dev. 2011; 21(4):422-30.
• Vicente-Crespo M and Palacios IM (2010) “Nonsense-mediated mRNA decay and Development:shoot the messenger to survive?” Biochemical Society Transactions Dec;38(6):1500-5.
• Loiseau P, Davies T, Williams LS, Mishima M, and Palacios IM. (2010) “Drosophila Pat1 is required for Kinesin-1 to transport cargo and to maximize its motility”. Development 137, 2763-2772
• Meignin C, Alvarez-Garcia I, Davis I, Palacios IM. (2007). "The salvador-warts-hippo pathway is required for epithelial proliferation and axis specification in Drosophila". Current Biology. Nov; 17(21):1871-8.
• Dispatch in Current Biology 17, Issue 23 (2007)
• Palacios IM. (2007). "How does an mRNA find its way? Intracellular localisation of transcripts". Seminars in Cell and Developmental Biology. Apr;18(2):163-170.
• Palacios IM, Gatfield D, St Johnston D and Izaurralde E (2004). An eIF4AIII-containing complex required for mRNA localisation and nonsense-mediated mRNA decay. Nature 427:753-757.
• News and Views, Nature Cell Biology 6, 285 - 287 (2004)
• Macchi P., Kroening S., Palacios IM., Baldassa S., Grunewald B., Ambrosino C., Lupas A., St Johnston D. and Kiebler M. (2003). Barentsz, a new component of the Staufen-containing ribonucleoprotein particles in mammalian cells, interacts with Staufen in a RNA-dependent manner. Journal of Neuroscience 23(13):5778-5788.
• Palacios IM. (2002). RNA Processing: Splicing and the cytoplasmic localisation of mRNA. Current Biology 12:50-52.
• Palacios IM. and 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(23):5473-5485.
• Benton, R, Palacios IM. and St Johnston D. (2002). Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation. Developmental Cell 3(5):659-671.
• Palacios, IM. and St Johnston D. (2001). Getting the Message Across: The Intracellular Localization of mRNAs in Higher Eukaryotes. Annual Review of Cell and Developmental Biology 17:569-614.
• van Eeden, FJM., Palacios IM., Petronczki M., Weston M., and St Johnston D. (2001). Barentsz is essential for the posterior localization of oskar mRNA and co-localizes with it to the posterior pole. Journal of Cell Biology 154:511-523.
• Wagner C., Palacios I., Jaeger L., St Johnston D., Ehresmann B., Ehresmann C., and Brunel C. (2001). Dimerization of the 3'UTR of bicoid mRNA Involves a Two-step Mechanism. Journal of Molecular Biology 313(3):511-524.
• Palacios, I. and Izaurralde, E. (2000). RNA transport and localisation. Encyclopedia Life Sciences, (Nature & MacMillan Publishers) (http://www.els.net)