miCLIP (methylation iCLIP)
motor neuron disease
Jernej obtained his BSc in Molecular Biology from University of Ljubljana, Slovenia, in 1999, and PhD in Molecular Neuroscience from Rockefeller University, New York, in 2004. After two-year postdoctoral work at Rockefeller University, he started his research group at the Structural Studies department of MRC Laboratory of Molecular Biology in Cambridge in August 2006. In April 2013, his group relocated to the Department of Molecular Neuroscience at the UCL Institute of Neurology. Since August 2016, the whole group has been seconded to The Francis Crick Institute in London. He serves on the editorial board of Genome Biology, is an EMBO fellow, and a member of the EMBO Course Committee.
Our research focuses on ‘regulatory RNPs’, which guide the RNA through the various regulatory stages from nucleus to the cytoplasm. Cells can change their gene expression by modulating the function of RNPs. Moreover, genetic studies have identified mutations that disrupt the normal function of RNPs. These mutations often cause neurologic diseases, particularly the motor neuron disease, also referred to as amyotrophic lateral sclerosis (ALS). We wish to understand how these mutations affect the assembly of protein-RNA complexes, thereby initiating the molecular cascade leading to disease.
To understand how regulatory RNPs work, we develop techniques that integrate biochemistry and computational biology to obtain a comprehensive map of protein-RNA interactions within our cells. We developed the individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP), and a related method called hiCLIP, which identify protein-RNA and RNA-RNA interactions with nucleotide resolution across the transcriptome. We use these methods to study how the sequence, structure and methylation of RNAs defines the assembly of RNPs, and how the regulatory RNPs in turn guide the life cycle of each RNA.
Jan Attig*, Federico Agostini, Clare Gooding, Anob M Chakrabarti, Julian A Zagalak, Aarti Singh, Nejc Haberman, Warren Emmett, Christopher WJ Smith, Nicholas M Luscombe, Jernej Ule*(2018) Heteromeric RNP assembly at LINEs controls lineage-specific RNA processing, Cell, Jul 31
Rot G*, Wang Z, Huppertz I, Modic M, Lenče T, Hallegger M, Haberman N, Curk T, von Mering C, Ule J*. (2017) High-Resolution RNA Maps Suggest Common Principles of Splicing and Polyadenylation Regulation by TDP-43. Cell Reports.May 2;19(5):1056-1067.
Haberman N*, Huppertz I*, Attig J, König J, Wang Z, Hauer C, Hentze MW, Kulozik AE, Le Hir H, Curk T, Sibley CR, Zarnack K*, Ule J* (2017) Insights into the design and interpretation of iCLIP experiments, Genome biology, Jan 16;18(1):7.
Attig J, Ruiz de Los Mozos I, Haberman N, Wang Z, Emmett W, Zarnack K, König J*, Ule J*(2016) Splicing repression allows the gradual emergence of new Alu-exons in primate evolution. Elife. Nov 18;5
SibleyRC*, EmmettW*, BlazquezL, FaroA, HabermanN, BrieseM, TrabzuniD, RytenM, HardyJ, UK Brain Expression Consortium, ModicM, CurkT, WilsonSW, PlagnolV*, Ule J*(2015) Recursive splicing in long vertebrate genes. Nature, May 21;521(7552):371-5.
Sugimoto Y, Vigilante A, Darbo E, Zirra A, Militti C,D’Ambrogio A, Luscombe N*, Ule J*(2015)hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1. Nature, Mar 26;519(7544):491-4.
Hussain S, Sajini AA, Blanco S, Dietmann S, Lombard P, Sugimoto Y, Paramor M, Gleeson JG, Odom DT, Ule J*, Frye M*. (2013) NSun2-Mediated Cytosine-5 Methylation of Vault Noncoding RNA Determines Its Processing into Regulatory Small RNAs. Cell Rep. Jul 25;4(2):255-61
Zarnack K*, König J*, Tajnik M, Martincorena I, Stévant I, Reyes A, Anders S, Luscombe NM*, Ule J* (2013) Direct competition between hnRNP C and U2AF65 protects the transcriptome from the uncontrolled exonization of Aluelements. Cell, Jan 31;152(3):453-66
Sugimoto Y, König J, Hussain S, Zupan B, Curk T, Frye M, Ule J (2012) Analysis of CLIP and iCLIP methods for nucleotide-resolution studies of protein-RNA interactions. Genome Biology, Aug 3;13(6):R67.
Tollervey JR*, Curk T*, Rogelj B*, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE, Ule J. (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci;14(4):452-8.
Wang Z*, Kayikci M*, Briese M, Zarnack K, Luscombe NM, Gregor R, Zupan B, Curk T, Ule J (2010) iCLIP predicts the dual splicing effects of TIA-RNA interactions, PLoS Biol.26;8(10):e1000530.
Konig J*, Zarnack K*, Curk T, Gregor R, Kayikci M, Zupan,B, Luscombe NM, Ule J (2010) iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution, Nat. Struct. Mol. Biol., Jul;17(7):909-15