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For the full list of publications, click here

Primary research publications

*Co--corresponding authors are marked by a star.

 

Miha Modic, Klara Kuret, Sebastian Steinhauser, Rupert Faraway, Emiel van Genderen, Flora Lee, Igor Ruiz de Los Mozos, Žiga Vičič, Jona Novljan, Derk ten Berge, Nicholas Luscombe, Jernej Ule (2024) Poised PABP-RNA hubs implement signal-dependent mRNA decay in development, Nature Str Mol Biol, Jul 25


Iosub IA, Wilkins OG, Ule J. (2024) Riboseq-flow: A streamlined, reliable pipeline for ribosome profiling data analysis and quality control. Wellcome Open Res. Apr 11;9:179


West C, Capitanchik C, Cheshire C, Luscombe NM, Chakrabarti A, Ule J. (2023) nf-core/clipseq - a robust Nextflow pipeline for comprehensive CLIP data analysis. Wellcome Open Res. Jul 4;8:286. doi: 10.12688/wellcomeopenres.19453.1. eCollection 2023.


Kuret K, Amalietti AG, Jones DM, Capitanchik C, Ule J. (2022) Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP. Genome Biol. Sep 9;23(1):191.
 

Chakrabarti AM, Capitanchik C, Ule J, Luscombe NM. (2023) clipplotr - a comparative visualisation and analysis tool for CLIP data. RNA. 2023 Mar 9

Rafiee MR, Rohban S, Davey K, Ule J, Luscombe NM. (2023) RNA polymerase II-associated proteins reveal pathways affected in VCP-related amyotrophic lateral sclerosis. Brain. Feb 15

Chakrabarti AM, Iosub IA, Lee FCY, Ule J, Luscombe NM. (2023) A computationally-enhanced hiCLIP atlas reveals Staufen1-RNA binding features and links 3' UTR structure to RNA metabolism. Nucleic Acids Res. Apr 4

Kuret K, Amalietti AG, Jones DM, Capitanchik C, Ule J. (2022) Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP. Genome Biol. Sep 9;23(1):191.

Rafiee MR*, Zagalak JA, Sidorov S, Steinhauser S, Davey K, Ule J*, Luscombe NM* (2021) Chromatin-contact atlas reveals disorder-mediated protein interactions and moonlighting chromatin-associated RBPs. Nucleic Acids Res. Dec 16;49(22):13092-13107.

Gameiro PA*, Encheva V, Dos Santos MS, MacRae JI, Ule J* (2021) Metabolic turnover and dynamics of modified ribonucleosides by 13C labeling. J Biol Chem. Nov;297(5):101294

Hallegger M*, Chakrabarti AM, Lee FCY, Lee BL, Amalietti AG, Odeh HM, Copley KE, Rubien JD, Portz B, Kuret K, Huppertz I, Rau F, Patani R, Fawzi NL, Shorter J, Luscombe NM, Ule J.* (2021) TDP-43 condensation properties specify its RNA-binding and regulatory repertoire. Cell. 2021 Sep 2;184(18):4680-4696.e22.

Wilkins OG, Capitanchik C, Luscombe NM, Ule J. (2021) Ultraplex: A rapid, flexible, all-in-one fastq demultiplexer. Wellcome Open Res. Jun 7;6:141. doi: 10.12688/wellcomeopenres.16791.1. eCollection 2021.

Strittmatter LM, Capitanchik C, Newman AJ, Hallegger M, Norman CM, Fica SM, Oubridge C, Luscombe NM, Ule J, Nagai K. (2021)

psiCLIP reveals dynamic RNA binding by DEAH-box helicases before and after exon ligation.

Nat Commun. Mar 5;12(1):1488. 

 

Briese M, Haberman N, Sibley CR, Faraway R, Elser AS, Chakrabarti AM, Wang Z, König J, Perera D, Wickramasinghe VO, Venkitaraman AR, Luscombe NM, Saieva L, Pellizzoni L, Smith CWJ, Curk T, Ule J. (2019)

A systems view of spliceosomal assembly and branchpoints with iCLIP.

Nat Struct Mol Biol. Sep 30. doi: 10.1038/s41594-019-0300-4.

Miha Modic, Markus Grosch, Gregor Rot, Tjasa Lepko, Tomohiro Yamazaki, Dmitry Shaposhnikov, Davide Cacchiarelli, Ejona Rusha, Boris Rogelj, Stefanie M. Hauck, Christian von Mering, Alexander Meissner, Tetsuro Hirose, Jernej Ule*, Micha Drukker* (2019)

Cross-regulation between TDP-43 and paraspeckles promotes pluripotency-differentiation transition, 

Mol Cell, Jun 6;74(5):951-965.e13

 

Lorea Blazquez*, Warren Emmett, Rupert Faraway, Simon Bajew, Andre Gohr, Nejc Haberman, Christopher R Sibley, Manuel Irimia, Jernej Ule* (2018)

Exon junction complex shapes the transcriptome by repressing recursive splicing,

Mol Cell, Nov 1;72(3):496-509.e9

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-43Cell Reports. May 2;19(5):1056-1067.

Lilach Soreq, UK Brain Expression Consortium, North American Brain Expression Consortium, Jamie Rose, Eyal Soreq, John Hardy, Daniah Trabzuni, Mark R. Cookson, Colin Smith, Mina Ryten, Rickie Patani*, Jernej Ule* (2017) 

Major shifts in glial regional identity are a transcriptional hallmark of human brain aging

Cell Reports, Jan 10;18(2):557-570

 

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

 

Sibley RC, Emmett W, Blazquez L, Faro A, Haberman N, Briese M, Trabzuni D, Ryten M, Hardy J, UK Brain Expression Consortium, Modic M, Curk T, Wilson SW, Plagnol V*, Ule J* (2105)
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* (2105)
hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1

Nature, Mar 26;519(7544):491-4.

 

Cereda M, Pozzoli U, Rot G, Juvan P, Schweitzer A, Clark T, Ule J. (2014)
RNA motifs: prediction of multivalent RNA motifs that control alternative splicing

Genome Biol. Jan 31;15(1):R20.

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, Eustermann S, 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 Alu elements. 

Cell, Jan 31;152(3):453-66

Rogelj B, Easton LE, Bogu GK, Stanton LW, Rot G, Curk T, Zupan B, Sugimoto Y, Modic M, Haberman N, Tollervey J, Fujii R, Takumi T, Shaw CE*, Ule J.* (2012)
Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain.,
Sci Rep. 2:603., Aug 28.

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.

McGlincy NM, Valomon A, Chesham JE, Maywood ES, Hastings MH*, Ule J* (2012)
Regulation of Alternative Splicing by the Circadian Clock and Food Related Cues,
Genome Biology, Jun 21;13(6):R54.

Tollervey JR, Wang Z., Hortobágyi T, Witten J., Zarnack K., Kayikci M, Clark TA, Schweitzer AC, Rot G, Curk T, Zupan B, Rogelj B, Shaw CE, Ule J. (2011)
Analysis of alternative splicing associated with aging and neurodegeneration in the human brain,
Genome Research, Aug 16, Supplementary

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. Apr;14(4):452-8. Epub 2011 Feb 27.

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 (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., 2010 Jul;17(7):909-15

Nejc J, Ule J*, Marko Z, Darnell RB (2007)
Evolution of Nova-dependent splicing regulation in the brain,
PLoS Genetics, 2007 Oct 12;3(10)

Ule, J, Stefani, G, Mele, A, Ruggiu, M, Wang, X, Taneri, B, Gaasterland, T, Blencowe, BJ, Darnell, RB (2006)
An RNA map predicting Nova-dependent splicing regulation,
Nature. 444(7119):580-6

Ule J, Ule A, Spencer J, Williams A, Hu JS, Cline M, Wang H, Clark T, Fraser C, Ruggiu M, Zeeberg BR, Kane D, Weinstein JN, Blume J, Darnell RB (2005)
Nova regulates brain-specific splicing to shape the synapse.
Nat Genet. Aug;37(8):844-52

Ule J, Jensen KB, Ruggiu M, Mele A, Ule A, Darnell RB (2003)
CLIP identifies Nova-regulated RNA networks in the brain.
Science. Nov 14;302(5648):1212-5

Method papers

Sugimoto Y, Chakrabarti AM, Luscombe NM, Ule J. (2017) 
Using hiCLIP to identify RNA duplexes that interact with a specific RNA-binding protein. 
Nat Protoc. 2017 Mar;12(3):611-637.

Huppertz I, Attig J, D'Ambrogio A, Eastonb L, Sibley CR, Sugimoto Y, Tajnik M, König J, Ule J. (2013)
iCLIP: Protein-RNA interactions at nucleotide resolution.
Methods. Oct 24.

Konig J, Zarnack K, Rot G, Curk T, Kayikci M, Zupan B, Turner DJ, Luscombe NM, Ule J. (2011)
iCLIP - Transcriptome-wide Mapping of Protein-RNA Interactions with Individual Nucleotide Resolution.
J Vis Exp. Apr 30;(50)

Wang Z, Tollervey J, Briese M, Turner D, Ule J. (2009)
CLIP: Construction of cDNA libraries for high-throughput sequencing from RNAs cross-linked to proteins in vivo.
Methods. 48(3):287-93.

Ule J, Jensen K, Mele A, Darnell RB. (2005)
CLIP: a method for identifying protein-RNA interaction sites in living cells.
Methods. Dec;37(4):376-86.

Reviews

Hafner M, Katsantoni M, Köster T, Marks T, Mukherjee J, Staiger D, Ule J*, Zavolan M (2021)

CLIP and complementary methods

Nature Reviews Methods Primers, volume 1, 20

Capitanchik C, Toolan-Kerr P, Luscombe NM, Ule J.

How Do You Identify m6 A Methylation in Transcriptomes at High Resolution? A Comparison of Recent Datasets.

Front Genet. 2020 May 20;11:398.

Ule J, Blencowe BJ. (2019) Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution.

Mol Cell. 2019 Oct 17;76(2):329-345

 

Ule J, Hwang HW, Darnell RB. (2018) The Future of Cross-Linking and Immunoprecipitation (CLIP). Cold Spring Harb Perspect Biol. Aug 1;10(8).

Anob M. Chakrabarti, Nejc Haberman, Arne Praznik, Nicholas M. Luscombe, and Jernej Ule (2018) 
Data Science Issues in Studying Protein–RNA Interactions with CLIP Technologies
Annual Reviews in Data Science, Vol. 1:235-261

Lee FCY, Ule J. (2018) Advances in CLIP Technologies for Studies of Protein-RNA Interactions
Mol Cell. Feb 1;69(3):354-369.

Skalska L, Beltran-Nebot M, Ule J*, Jenner RG* (2017)
Regulatory feedback from nascent RNA to chromatin and transcription. 
Nat Rev Mol Cell Biol. 2017 Mar 8.

Sibley RC, Blazquez L, Ule J (2016) 
Lessons from non-canonical splicing.
Nature Reviews Genetics Jul;17(7):407-21

Rinn JL, Ule J. (2014) 
'Oming in on RNA-protein interactions.
Genome Biol. Jan 31;15(1):401.

Ule J. (2013)
Alu elements: at the crossroads between disease and evolution.
Biochem Soc Trans. Dec 1;41(6):1532-5.

Kiebler MA, Scheiffele P, Ule J. (2013)
What, where, and when: the importance of post-transcriptional regulation in the brain.
Front Neurosci. Oct 29;7:192.

Modic M, Ule J*, Sibley CR*. (2013)
CLIPing the brain: Studies of protein-RNA interactions important for neurodegenerative disorders.
Mol Cell Neurosci Apr 10

Sibley CR*, Attig J*, Ule J. (2012)
The greatest catch: big game fishing for mRNA-bound proteins..
Genome Biology, Jul 17;13(7):163.

Patani R., Sibley C.R., Chandran S., Ule J. (2012)
Using human pluripotent stem cells to study post-transcriptional mechanisms of neurodegenerative diseases..
Brain Res., Jan 5

König J., Zarnack K., Luscombe N. M., Ule J. (2012)
Protein–RNA interactions: new genomic technologies and perspectives..
Nature review genetics, Jan 21;13(2):77-83.

Witten, JT, Ule J. (2011)
Genome-wide studies of splicing regulation by RNA-binding proteins.
Trends in Genetics, Mar;27(3):89-97.

Ule J. (2009)
High-throughput sequencing methods to study neuronal RNA-protein interactions.
Biochem Soc Trans. 37(Pt 6):1278-80.

Ule J. (2008)
Ribonucleoprotein complexes in neurologic diseases.
Curr Opin Neurobiol. Oct;18(5):516-23.

Ule J, Darnell RB (2006)
RNA-binding proteins in neuronal development in disease,
Curr. Opin. Neurobiol, 2006 Feb;16(1):102-10

Book contributions

König J., McGlincy N.J., Ule J. (2012)
Analysis of protein-RNA interactions with single-nucleotide resolution using iCLIP and Next Generation Sequencing.,
Tag-based Next Generation Sequencing, Wiley, Matthias Harbers (Ed.), Guenter Kahl (Ed.)

König J., McGlincy N.J., Ule J. (2012)
Global analysis of protein-RNA interactions with single-nucleotide resolution using iCLIP,
Handbook of RNA Biochemistry, Wiley, Roland Hartmann (ed.)

Tollervey, J. and Ule, J. (2012)
The CLIP Method to Study Protein–RNA Interactions in Intact Cells and Tissues,
Alternative pre-mRNA Splicing: Theory and Protocols (eds S. Stamm, C. W. J. Smith and R. Lührmann), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany.

Rogelj, B., Godin, KS, Shaw CE, Ule J (2011)
The Functions of glycine‑rich regions in TDP‑43, FUS and related RNA‑binding proteins,
RNA Binding Proteins, Landesbioscience. Series: Special Books, Lorkovic Zdravko (Ed.)

Ule J, Darnell RB (2008)
Functional and mechanistic insights from genome-wide studies of splicing regulation in the brain,
Alternative Splicing in the Postgenomic Era, Landesbioscience, Series: Advances in Experimental Medicine and Biology, Vol. 623, Blencowe, Benjamin J.; Graveley, Brenton R. (Eds.)

Journal issues

A 2013 issue of the Frontiers in Neuroscience, dedicated to the post-transcriptional regulation in the brain.

An issue of Genome Biology, dedicated to RBPome.

An issue of Methods, dedicated to protein-RNA interactions, including manuscripts on CLIP and related experimental and computational methods.

Summaries of selected publications

 

Modic et al. (2024) Poised PABP-RNA hubs implement signal-dependent mRNA decay in development, Nature Str Mol Biol, Jul 25

How can cellular signalling quickly change the set of expressed genes (transcriptome) to drive fast biological changes? We used deep learning and a range of systems-biology techniques to discover dynamic RNA binding patterns, or ‘mRNA hubs’, at the ends of mRNAs that control a developmental cell fate transition. These mRNA hubs undergo major changes in ribonucleoprotein assembly upon ERK signalling. This signalling leads to phosphorylation of the protein LIN28A, which then converges within mRNA hubs with another protein, PABP, to induce selective decay of mRNAs which are no longer needed to maintain pluripotent cell fate. This is required for progression of early development. This is a great example of productive collaboration between the researchers in Ljubljana and London, more from Miha on the paper here.

Kuret K, Amalietti AG, Jones DM, Capitanchik C, Ule J. (2022) Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP. Genome Biol. Sep 9;23(1):191.

We previously developed iCLIP, a method to efficiently identify sites of protein-RNA crosslinking across the transcriptome. However, these crosslink sites don't necessarily align with all the RNA sequence motifs that are recognised by proteins to drive their binding specificity. We therefore developed new software, positionally-enriched k-mer analysis (PEKA, available here), which enables user-friendly detection of enriched RNA motifs from individual CLIP datasets and visualizes their positional profiles around crosslink sites. We also showed how CLIP meta-analyses can yield insights into the extent and specificity of motif enrichment in each dataset, and provide such analysis of ENCODE eCLIP for exploratory analysis in an RBP-centric and motif-centric manner. This is the first manuscript fully done by the Ljubljana satellite, led by the PhD student Klara.

Hallegger et al, TDP-43 condensation properties specify its RNA-binding and regulatory repertoire Cell. 2021 Sep 2;184(18).

Many neurodegenerative diseases are associated with formation of toxic aggregates of TDP-43, which result from the strong propensity of TDP-43 for molecular condensation. We addressed the long-standing question of whether such condensation propensity affects its RNA binding specificity and function. We created variants of TDP-43 with a gradient of condensation properties and used comparative iCLIP to find its roles in binding to long RNA regions that contain widely dispersed binding motifs, a phenomenon we refer to as ‘binding region condensates’. Thereby, TDP-43 regulates a select subset of 3’UTR isoforms, including autoregulation of TDP-43 itself. Our study thus shows that changes in TDP-43 condensation can deregulate a selective subset of RNAs, which could contribute to the early stages of neurodegenerative diseases. More from Martina on the paper here.

Strittmatter et al, psiCLIP reveals dynamic RNA binding by DEAH-box helicases before and after exon ligation. Nat Commun. 2021 Mar 5;12(1):1488.

After a fruitful collaboration with the Kiyoshi Nagai lab we bring you psiCLIP - a method for profiling helicase-RNA contacts in defined spliceosome states. Led by Lisa Strittmatter & Charlotte Capitanchik, and with fantastic insights from Sebastian Fica

Studies of spliceosomal interactions are challenging due to their dynamic nature. We have previously established spliceosome iCLIP to map spliceosome engagement with pre-messenger RNAs in human cell lines. We now present a variant applicable to purified spliceosome: psiCLIP (purified spliceosome individual nucleotide resolution Cross-Linking and ImmunoPrecipitation), which involves first stalling and purifying the spliceosome at specific stages. Thereby, we investigate how Prp16 and Prp22 engage their RNA substrate at defined points in the splicing pathway. The wet-lab method is accompanied by an open source bioinformatics pipeline written in Snakemake https://github.com/luslab/psiclip. Read more about it in the LMB news.

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