Background: Postdoctoral work with Professor Don Rio (2006 - 2011), University California, Berkeley; Post-doctoral work with Professor Juan Pablo Couso, University of Sussex (2012 - 2015);
Contact: Garstang 9.56f, +44(0) 113 34 39607,
Julie read Biochemistry at The Queen’s College, Oxford before undertaking a PhD in Biochemistry at the University of Cambridge on the initiation of mRNA translation. During her first postdoc at the University of California, Berkeley, her work focused on alternative mRNA splicing in the fruit fly. Julie’s second postdoc was at the University of Sussex, where she defined novel regions of translation. In 2015 Julie was awarded a University Academic Fellowship in Pervasive Transcription reflected by her interest in the function and biological impact of RNAs. This fellowship allowed Julie to establish her own research group here at Leeds in August 2015.
Her group addresses questions on the regulation of mRNA translation, non-coding RNA function and the role of specific RNA-protein complexes. She combines biochemistry, genomics, molecular biology and genetics to study RNAs in fruit flies and mammalian tissue culture. Drosophila is an idea model for this work because it is amenable to genetic characterisations, suitable for biochemical purifications of material from organisms and tissue culture cells and the quality of genomic data available is excellent. Many of the regulatory processes and RNA-binding proteins are highly conserved between Drosophila and mammals.
mRNAs are at the centre of gene expression, providing translational machinery with a copy of the genetic code. Proteins interact with sequence elements within mRNAs to ensure accurate mRNA processing. The identity of proteins bound to mRNAs changes as they participate in different events. RNA-binding proteins interact with RNAs as soon as they are transcribed in the nucleus. Some of these interactions regulate nuclear RNA processing events such as splicing. Other RNA-binding proteins affect the translation of mRNAs as well eg. PTB. The extent to which these nuclear associations continue as mRNAs are exported from the nucleus to the cytoplasm is not yet clear. The changing composition of these complexes is likely to be highly regulated and affect to what extent mRNAs are translated into proteins. Our long-term goal is to understand how RNA processing in the nucleus affects translation in the cytoplasm and how disturbing mRNP composition can be detrimental to the cell.
Regulation of mRNA translation
Canonical initiation involves the recruitment of the 40S ribosome to the 5' end of the mRNA. The 40S then scans through the 5'-UTR to find the start codon, where the 60S joins and elongation begins. We are interested in how translation is regulated during initiation, especially by the 5'-UTR and associated proteins. Disruptions to RNA-protein interactions and translational regulation play significant roles in a variety of cancers and other disorders (e.g. spinal muscular atrophy).
Long non-coding RNAs in the cytoplasm
Whilst the majority of our genome is transcribed, only a small fraction is protein-coding. This implies that many non-coding RNAs exist, some of which are similarly processed to mRNAs, termed long non-coding RNAs (lncRNAs). The majority of characterised lncRNAs are nuclear but recent ribosome profiling results have revealed that many are translated. Although controversial, it is clear that numerous lncRNAs are cytoplasmic, polysome-associated and translated. The line between coding and non-coding has become blurred and some lncRNAs are really mRNAs. LncRNAs are enriched in neuronal tissues and several have been found associated with neurological conditions e.g. Alzheimer’s disease. To better understand the molecular basis of neuronal disease it is vital that we appreciate the role of cytoplasmic lncRNAs in regulating gene expression. We are studying the function of these cytoplasmic lncRNAs.
"Dissecting the molecular mechanisms of lncRNA function in X chromosome inactivation across mammalian gestation evolution"
"Structure and function of specialised ribosomes in neurons"
MRC DiMeN Doctoral Training Partnership Studentship
BIOC3160 - Laboratory/Literature/Computing Research Project
BIOC3221/22/BIOL3210/MICR3211 D - ATU - RNA binding proteins
BIOL3306 - Biological Sciences Research Project
BIOL5390M - Bioscience MSc Research Project
Group Leader Dr Julie Aspden (University Academic Fellowship in Pervasive Transcription)
Ms Tayah Hopes (Research Technician)
Dr Eleanor Walton (Research Fellow in RNA Biology)
Michaela Agapiou (Primary supervisor) 50% FTE
Aikaterini Douka (Primary supervisor) 50% FTE
Ioannis Tsagakis (Primary supervisor) 40% FTE
James Murphy (Co-supervisor) 50% FTE
Christian Nathan (Co-supervisor) 20% FTE
Aspden JL, Eyre-Walker YC, Phillips RJ, Amin U, Mumtaz MAS, Brocard M, Couso J-P Extensive translation of small Open Reading Frames revealed by Poly-Ribo-Seq Elife 3 -, 2014
Rogulja-Ortmann A, Picao-Osorio J, Villava C, Patraquim P, Lafuente E, Aspden J, Thomsen S, Technau GM, Alonso CR The RNA-binding protein ELAV regulates Hox RNA processing, expression and function within the Drosophila nervous system. Development 141 2046-2056, 2014
Taliaferro JM, Aspden JL, Bradley T, Marwha D, Blanchette M, Rio DC Two new and distinct roles for Drosophila Argonaute-2 in the nucleus: alternative pre-mRNA splicing and transcriptional repression. Genes Dev 27 378-389, 2013
Taliaferro JM, Marwha D, Aspden JL, Mavrici D, Cheng NE, Kohlstaedt LA, Rio DC The Drosophila splicing factor PSI is phosphorylated by casein kinase II and tousled-like kinase. PLoS One 8 e56401-, 2013
Brooks AN, Aspden JL, Podgornaia AI, Rio DC, Brenner SE Identification and experimental validation of splicing regulatory elements in Drosophila melanogaster reveals functionally conserved splicing enhancers in metazoans. RNA 17 1884-1894, 2011
Song EJ, Werner SL, Neubauer J, Stegmeier F, Aspden J, Rio D, Harper JW, Elledge SJ, Kirschner MW, Rape M The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome. Genes Dev 24 1434-1447, 2010
Aspden JL, Jackson RJ Differential effects of nucleotide analogs on scanning-dependent initiation and elongation of mammalian mRNA translation in vitro. RNA 16 1130-1137, 2010