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HITS-CLIP yields genome-wide insights into brain alternative RNA processing
Open accessAbstract
Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.
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“crosslinking and immunoprecipitation followed by high-throughput sequencing (HITS-CLIP) has been developed to isolate RNA fragments directly bound by an RBP of interest (Darnell, 2010; Licatalosi et al., 2008; Moore et al., 2014; Ule et al., 2005a).”
From HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism (2014) · cites this paper as Licatalosi et al., 2008
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“Indeed, dual functions for splicing regulators in 3′-end poly-A site selection and mRNA transport have been described26,27”
From A compendium of RNA-binding motifs for decoding gene regulation (2013) · cites this paper as [26]
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“Alternative splicing (AS) is a highly tissue-specific process18 that greatly increases the complexity of the potential set of RNA molecules produced from multi-exon genes.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [18]
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MethodRNase-assisted RNA chromatography
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“…cross-linking and immunoprecipitation (CLIP) (Ule et al. 2003, 2005), and its high-throughput sequencing derivatives (HITS-CLIP or CLIP-Seq) (Licatalosi et al. 2008; Reprint requests to: Gracjan Michlewski, Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh…”
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“This can be exploited through genomewide profiling of RBP in vivo target RNAs via advanced RNA immunoprecipitations such as individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) [74] or high throughput sequencing (HITS)-CLIP [75].”
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“For example, the KH-domain-binding protein Nova2, a protein closely related to CP, exerts controls over poly(A) site choices in a position-dependent manner (54).”
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“…sequencing (CLIP-seq) technologies, which combine immunoprecipitation with RNA – protein crosslinking followed by high-throughput sequencing, has enabled researchers to characterize transcriptome-wide RNA – protein binding sites with high resolution in different mammalian cells [12 – 14].”
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“Bands corresponding to smRNA-RBP interactions (no RNase digestion) or a smear representing mRNA-RBP interactions (low RNase digestion) by autoradiogram were processed for HITS-CLIP.”
InfluentialELAV/Hu RNA binding proteins determine multiple programs of neural alternative splicing
Lee, S., Wei, L., Zhang, B., Goering, R., Majumdar, S., Wen, J., Taliaferro, J. M., & Lai, E. C. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009439 · Cited by 46
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Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9
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“The RNA immunoprecipitation protocol described below is based on previously described assays (Conrad, 2008; Jensen and Darnell, 2008; Licatalosi et al., 2008).”
MethodVersatile interactions and bioinformatics analysis of noncoding RNAs
Chen, Q., Meng, X., Liao, Q., & Chen, M. (2018) · Briefings in Bioinformatics · doi:10.1093/bib/bby050 · Cited by 44
Identification of proteins and miRNAs that specifically bind an mRNA in vivo
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Defects in translational regulation contributing to human cognitive and behavioral disease
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Self-citationRIP-Seq Data Analysis to Determine RNA–Protein Associations
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Template-Based Modeling of Protein-RNA Interactions
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“High-throughput experimental techniques (HITS-CLIP [7], PAR-clip [8], RIP-chip [9]) and computational methods [10–18] have been developed to characterize protein-RNA interactome.”
MethodlncRedibly versatile: biochemical and biological functions of long noncoding RNAs
Shields, E. J., Petracovici, A., & Bonasio, R. (2019) · Biochemical Journal · doi:10.1042/bcj20180440 · Cited by 42
Post-transcriptional regulation of inflammation by RNA-binding proteins via cis-elements of mRNAs
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“One of the most important innovative techniques is the CLIP, which makes it possible for us to fully understand the target molecules of RBPs with high sensitivity (72, 73).”
Dehydration stress extends mRNA 3′ untranslated regions with noncoding RNA functions in ArabidopsisPreprint
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Stepwise assembly of the Nova -regulated alternative splicing network in the vertebrate brain
Irimia, M., Denuc, A., Burguera, D., Somorjai, I., Martín-Durán, J. M., Genikhovich, G., Jimenez-Delgado, S., Technau, U., Roy, S. W., Marfany, G., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012333108 · Cited by 47
“Nova regulates specific exons by binding to clusters of tetranucleotide [CU]CA[CU] (YCAY) motifs in exons or near splice sites in pre-mRNAs; depending on the position of Nova-binding sites relative to splice sites, Nova can either enhance or inhibit the inclusion of a particular exon in transcripts (12, 13).”
BackgroundCis-Acting Polymorphisms Affect Complex Traits through Modifications of MicroRNA Regulation Pathways
Arnold, M., Ellwanger, D. C., Hartsperger, M. L., Pfeufer, A., & Stümpflen, V. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036694 · Cited by 44
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“Future studies that compare HITS-CLIP [40] from Zar1 and Zar2 will help distinguish between Zar1 and Zar2 binding the same or different repertoires of maternal mRNAs.”
Computational Prediction of miRNA Genes from Small RNA Sequencing Data
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“In some cases, the interaction between protein and RNA is stabilized by crosslinking (Licatalosi et al., 2008; Hafner et al., 2010), and some studies also investigate interaction with other proteins known to interact with miRNAs, such as DGCR8 (Macias et al.”
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Alternative polyadenylation: An enigma of transcript length variation in health and disease
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“…general PA-site selection include HU protein, NOVA, CELF2, CNOT, FUS, MBNL, hnRNPC, and PTBP1 (Batra et al., 2014; Chatrikhi et al., 2019; Fischl et al., 2019; A. J. Gruber et al., 2018; A. J. Gruber et al., 2016; Jutzi et al., 2020; Licatalosi et al., 2008; Masuda et al., 2015; Romo et al., 2017).”
BackgroundFrom computational models of the splicing code to regulatory mechanisms and therapeutic implications
Capitanchik, C., Wilkins, O. G., Wagner, N., Gagneur, J., & Ule, J. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00774-2 · Cited by 45
Self-citationQuantitative mass spectrometry and PAR-CLIP to identify RNA-protein interactions
Scheibe, M., Butter, F., Hafner, M., Tuschl, T., & Mann, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks746 · Cited by 41
Leveraging cross-link modification events in CLIP-seq for motif discovery
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Alternative polyadenylation of antisense RNAs and flowering time control
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Zhang, Z., Bae, B., Dredge, W. H., & Miura, P. (2023) · Nature Communications · doi:10.1038/s41467-023-41207-8 · Cited by 40
“In fact, multiple RBPs that regulate AS have also been found to regulate APA 27 – 30 .”
Profiling of RNA-binding protein binding sites by in situ reverse transcription-based sequencing
Xiao, Y., Chen, Y.-M., Zou, Z., Ye, C., Dou, X., Wu, J., Liu, C., Liu, S., Yan, H., Wang, P., et al. (2024) · Nature Methods · doi:10.1038/s41592-023-02146-w · Cited by 39
“S 10 -len 5,6,7,8,9.”
The role of SON in splicing, development, and disease
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Analysis of the mRNA Targetome of MicroRNAs Expressed by Marek’s Disease Virus
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Toward a combinatorial nature of microRNA regulation in human cells
Balaga, O., Friedman, Y., & Linial, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks759 · Cited by 39
“TargetScan, Supplementary Figure S3) and the union of the MDBs differ from the properties of the CLIP data (24,27,67,68) (Supplementary Figure S3).”
BackgroundStefani, G., Chen, X., Zhao, H., & Slack, F. J. (2015) · RNA · doi:10.1261/rna.045542.114 · Cited by 40
Illustrating the interplay between the extracellular matrix and micro RNA s
Piccinini, A. M., & Midwood, K. S. (2014) · International Journal of Experimental Pathology · doi:10.1111/iep.12079 · Cited by 41
“Optimization of the IP in order to stabilize the RNA-protein binding has led to the development of high-throughput sequencing of RNAs isolated by cross-linking IP (HITS-CLIP) and, more recently, photoactivatableribonucleoside-enhanced cross-linking and IP (PAR-CLIP; Licatalosi et al. 2008; Hafner et al. 2010).”
MethodDrosophila Imp iCLIP identifies an RNA assemblage coordinating F-actin formation
Hansen, H. T., Rasmussen, S. H., Adolph, S. K., Plass, M., Krogh, A., Sanford, J. R., Nielsen, F. C., & Christiansen, J. (2015) · Genome biology · doi:10.1186/s13059-015-0687-0 · Cited by 42
“In this way, novel details of DGCR8 (DiGeorge syndrome critical region 8) functions [19], regulation of splicing [16, 20], and alternative polyadenylation [21] have been elucidated.”
BackgroundMicroRNA target prediction using thermodynamic and sequence curves
Ghoshal, A., Shankar, R., Bagchi, S., Grama, A. Y., & Chaterji, S. (2015) · BMC Genomics · doi:10.1186/s12864-015-1933-2 · Cited by 41
“, 3’ end) and, to a lesser degree, near stop codons (5’ end), than in the middle of 3’ UTR regions, as reported in [17].”
BackgroundBiological functions, regulatory mechanisms, and disease relevance of RNA localization pathways
Bovaird, S., Patel, D., Padilla, J.-C. A., & Lécuyer, É. (2018) · FEBS Letters · doi:10.1002/1873-3468.13228 · Cited by 40
Multi-Omics Approaches to Study Long Non-coding RNA Function in Atherosclerosis
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RNA binding proteins: a common denominator of neuronal function and dysfunction
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“formation of the cleavage complex([63]).”
BackgroundResultInfluentialToward a systems view on RNA-binding proteins and associated RNAs in plants: Guilt by association
Mateos, J. L., & Staiger, D. (2022) · The Plant Cell · doi:10.1093/plcell/koac345 · Cited by 39
Global insights into alternative polyadenylation regulation
Batra, R., Manchanda, M., & Swanson, M. S. (2015) · RNA Biology · doi:10.1080/15476286.2015.1040974 · Cited by 41
“The neuron specific splicing factor, NOVA2, plays a crucial role in tissue-specific AS and APA regulation in the brain.(32) Both PTB and hnRNP H have also been reported to regulate both AS and APA.”
BackgroundHennig, J., & Sattler, M. (2015) · BioEssays · doi:10.1002/bies.201500033 · Cited by 37
“Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data.”
BackgroundMethodInfluentialmiRNA in Pluripotent Stem Cells
Lakshmipathy, U., Davila, J., & Hart, R. P. (2010) · Regenerative Medicine · doi:10.2217/rme.10.34 · Cited by 39
“For example, Darnell and co-workers have developed a method called high-throughput sequencing-cross-linking immunoprecipitation (HITS-CLIP) [57–59] in which RNA-protein complexes are crosslinked in situ, partially digested with RNAase to trim away RNA that does not interact with the protein, and then immunoprecipitate…”
MethodInconsistencies and Limitations of Current MicroRNA Target Identification Methods
Mockly, S., & Seitz, H. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9207-2_16 · Cited by 42
Nucleotide-amino acid π-stacking interactions initiate photo cross-linking in RNA-protein complexes
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Probing RNA–protein networks: biochemistry meets genomics
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Genome-Wide Mapping of Cellular Protein–RNA Interactions Enabled by Chemical Crosslinking
Li, X., Song, J., & Yi, C. (2014) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2014.03.001 · Cited by 40
“HITS-CLIP was first applied to study Nova–RNA interactions and uncovered the 3’ end RNA processing rules in the brain [8].”
MethodAlternative polyadenylation and RNA-binding proteins
Erson-Bensan, A. E. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0070 · Cited by 39
Emerging Themes in Regulation of Global mRNA Turnover in cis
Chen, C. A., & Shyu, A. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.08.014 · Cited by 42
“For example, in brain and nervous tissues, mRNA transcripts tend to use poly(A) sites that are distal to the stop codon, leading to mRNA isoforms with longer 30 UTRs [77,78].”
BackgroundBenhalevy, D., McFarland, H. L., Sarshad, A. A., & Hafner, M. (2016) · Methods · doi:10.1016/j.ymeth.2016.11.009 · Cited by 38
Footprinting SHAPE-eCLIP Reveals Transcriptome-wide Hydrogen Bonds at RNA-Protein Interfaces
Corley, M., Flynn, R. A., Lee, B., Blue, S. M., Chang, H. Y., & Yeo, G. W.-M. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.11.014 · Cited by 36
“Immunoprecipitation techniques have identified transcripts or portions of transcripts bound by hundreds of RBPs of interest, but these lack the resolution to study the precise nucleotides that interact with proteins (Colombrita et al., 2012; Hafner et al., 2010; Licatalosi et al., 2008; Van Nostrand et al., 2016).”
BackgroundZhao, Z., Xu, Q., Wei, R., Wang, W., Ding, D., Yang, Y., Yao, J., Zhang, L., Hu, Y., Wei, G., et al. (2021) · Genome Research · doi:10.1101/gr.271627.120 · Cited by 40
“…repressors, andmultiple RNA-binding proteins (RBPs) can protect the transcriptome from the aberrant exonization of transposable elements (Zarnack et al. 2013; Attig et al. 2018) and modulate cleavage and polyadenylation at poly(A) sites where they bind (Licatalosi et al. 2008; Hilgers et al. 2012).”
BackgroundZhang, H., Liang, Y., Han, S., Peng, C., & Li, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061284 · Cited by 38
“Several large-scale experimental approaches for lncRNA–protein interaction prediction include RNAcompete [18], RNP immunoprecipitation-microarray (RIP-Chip) [19], high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) [20] and photoactivatable ribonucleoside-enhanced crosslinking an…”
BackgroundEfficiently identifying genome-wide changes with next-generation sequencing data
Huang, W., Umbach, D. M., Jordan, N. V., Abell, A. N., Johnson, G. L., & Li, L. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr592 · Cited by 37
“In addition, mRNA-seq is being used to interrogate post-transcriptional gene regulation including the control of alternative splicing (15) and polyadenylation (16), RNA editing (17) and degradation and translation of mRNA.”
MethodFine-tuning the brain: MicroRNAs
Vreugdenhil, E., & Berezikov, E. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.08.001 · Cited by 36
“[30] or crosslinking and immunoprecipitation followed by high throughput sequencing (CLIP-seq; [27,48], are needed to address this issue.”
BackgroundMicroRNA Screening and the Quest for Biologically Relevant Targets
Eulálio, A., & Mano, M. (2015) · SLAS DISCOVERY · doi:10.1177/1087057115578837 · Cited by 37
Predicting lncRNA–Protein Interactions With miRNAs as Mediators in a Heterogeneous Network Model
Zhou, Y.-K., Shen, Z.-A., Yu, H., Luo, T., Gao, Y., & Du, P.-F. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2019.01341 · Cited by 37
Tan, J. Y., & Marques, A. C. (2014) · Advances in genetics · doi:10.1016/b978-0-12-800271-1.00003-2 · Cited by 37
“For instance, the DIANA-LncBase (Paraskevopoulou et al., 2013) integrates putative MREs on the GENCODE-annotated lncRNAs determined using HITS-CLIP and PAR-CLIP experimental data and MREs predicted using miRcode (Jeggari, Marks, & Larsson, 2012).”
MethodHiguera, G. A., Hendriks, J., van Dalum, J., Wu, L., Schotel, R., Teixeira, L. M., van den Doel, M., Leijten, J., Riesle, J., Karperien, M., et al. (2013) · Integrative Biology · doi:10.1039/c3ib40023a · Cited by 36
Argonaute CLIP – A method to identify in vivo targets of miRNAs
Jaśkiewicz, Ł., Bilen, B., Hausser, J., & Zavolan, M. (2012) · Methods · doi:10.1016/j.ymeth.2012.09.006 · Cited by 36
Cole, B. S., Tapescu, I., Allon, S. J., Mallory, M. J., Qiu, J., Lake, R. J., Fan, H.-Y., Fu, X., & Lynch, K. W. (2015) · RNA · doi:10.1261/rna.052969.115 · Cited by 34
“Importantly, tissue-specific differences in alternative splicing (AS) have been suggested to shape cell-fate decisions (Gehman et al. 2012; Licatalosi et al. 2012; Xue et al. 2013; Raj et al. 2014; Quesnel-Vallieres et al. 2015), while signal-in- duced changes in AS have been observed in response…”
BackgroundBottini, S., Hamouda‐Tekaya, N., Tanasă, B., Zaragosi, L., Grandjean, V., Repetto, E., & Trabucchi, M. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx007 · Cited by 36
“CLIP-seq is a relatively new experimental technique to study the specificity of the binding activity for RNABinding Proteins (RBP) (9).”
BackgroundMethodInfluentialAlternative Splicing in Genetic Diseases: Improved Diagnosis and Novel Treatment Options
Bergsma, A. J., van der Wal, E., Broeders, M., van der Ploeg, A. T., & Pijnappel, W. W. M. P. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.07.008 · Cited by 42
Evidence of Aberrant Immune Response by Endogenous Double‐Stranded RNAs: Attack from Within
Kim, S., Ku, Y., Ku, J., & Kim, Y. (2019) · BioEssays · doi:10.1002/bies.201900023 · Cited by 34
Laurent, G. S., Savva, Y. A., & Kapranov, P. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00057 · Cited by 36
“…function in both cooperative and competitive types of architectures, as documented in splicing regulation (Darnell, 2006; Sharma and Black, 2006; Ule and Darnell, 2007; Licatalosi et al., 2008; Hallegger et al., 2010), and more recently in chromatin signaling (Tsai et al., 2010; Zhao et al., 2010).”
BackgroundMarc, D., Barbachou, S., & Soubieux, D. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks979 · Cited by 36
“Although high-throughput sequencing combined to a less stringent SELEX (49) or to a crosslinking method (50) would probably yield broader sets of ligands, our set of 63 Figure 8.”
BackgroundWolf, J. J., Dowell, R. D., Mahony, S., Rabani, M., Gifford, D. K., & Fink, G. R. (2010) · Genetics · doi:10.1534/genetics.110.113944 · Cited by 38
“The repeating CA pattern is similar to the one found in RNAs recognized by the mammalian RNA-binding protein Nova (Buckanovich and Darnell 1997; Jensen et al. 2000; Ule et al. 2003; Licatalosi et al. 2008).”
BackgroundMethodA Comparative Perspective on Wnt/β-Catenin Signalling in Cell Fate Determination
Garcin, C. L., & Habib, S. J. (2017) · Results and problems in cell differentiation · doi:10.1007/978-3-319-53150-2_15 · Cited by 40
RNA Binding Proteins as Pioneer Determinants of Infection: Protective, Proviral, or Both?
Lisy, S. M., Rothamel, K. L., & Ascano, M. (2021) · Viruses · doi:10.3390/v13112172 · Cited by 35
“Considerations for choosing a certain technique for a virus of interest include genomic structure, replication cycle, and cellular tropism, with additional criteria recently reviewed [59,105].”
BackgroundMethodTranscriptome-wide identification of RNA binding sites by CLIP-seq
Murigneux, V., Saulière, J., Crollius, H. R., & Hir, H. L. (2013) · Methods · doi:10.1016/j.ymeth.2013.03.022 · Cited by 39
Translational regulation in growth cones
Jung, H., O'Hare, C. M., & Holt, C. E. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2011.04.004 · Cited by 35
Cooperativity in RNA–protein interactions: the complex is more than the sum of its partners
Achsel, T., & Bagni, C. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.06.007 · Cited by 36
GoldCLIP: Gel-Omitted Ligation-Dependent CLIP
Gu, J., Wang, M., Yang, Y., Qiu, D., Zhang, Y., Ma, J., Zhou, Y., Hannon, G. J., & Yu, Y. (2018) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2018.04.003 · Cited by 35
“Various CLIP methods, such as high-throughput sequencing of RNA isolated by CLIP (HITS-CLIP) [4], photoactivatable ribonucleosideenhanced CLIP (PAR-CLIP) [5], individual-nucleotide resolution CLIP (iCLIP) [6], and their derivatives [7–9], have been developed to profile transcriptome-wide protein–RNA interactions.”
MethodKöster, T., Reichel, M., & Staiger, D. (2019) · Methods · doi:10.1016/j.ymeth.2019.09.005 · Cited by 35
TREND-DB—a transcriptome-wide atlas of the dynamic landscape of alternative polyadenylation
Marini, F., Scherzinger, D., & Danckwardt, S. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa722 · Cited by 35
“We depleted more than 170 proteins, including all known factors involved in pre-mRNA 3’end CPA in eukaryotes (8) and selected key factors regulating transcriptional activities, splicing, RNA turnover, and other functions (47; 48; 49; 50; 51; 52; 53; 54; 55; 56; 57; 58; 59) which could directly or indirectly affecting…”
BackgroundChu, L., Arêde, P., Li, W., Urdaneta, E. C., Ivanova, I., McKellar, S. W., Wills, J. C., Fröhlich, T., von Kriegsheim, A., Beckmann, B. M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30553-8 · Cited by 30
Improved binding site assignment by high-resolution mapping of RNA–protein interactions using iCLIP
Hauer, C., Curk, T., Anders, S., Schwarzl, T., Alleaume, A.-M., Sieber, J., Hollerer, I., Bhuvanagiri, M., Huber, W. K., Hentze, M. W., et al. (2015) · Nature Communications · doi:10.1038/ncomms8921 · Cited by 33
“4) and (2) completely sequenced fragments (group A, Fig.”
BackgroundResultInfluentialAllogeneic T cell responses are regulated by a specific miRNA-mRNA network
Sun, Y., Tawara, I., Zhao, M., Qin, Z. S., Toubai, T., Mathewson, N. D., Tamaki, H., Nieves, E. C., Chinnaiyan, A. M., & Reddy, P. R. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70013 · Cited by 34
“…biological activity (11, 45), a functional 3 ′ UTR located within 10 kb downstream of the annotated transcript and exons, and intron or noncoding locations with unknown function, all of which are not included or considered in the current computational algorithms for target prediction (11, 46, 47).”
Alternative polyadenylation and the stress response
Sadek, J., Omer, A., Hall, D. T., Ashour, K., & Gallouzi, I. (2019) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1540 · Cited by 34
Deng, L., Liu, Y., Shi, Y., Zhang, W., Yang, C., & Liu, H. (2020) · BMC Genomics · doi:10.1186/s12864-020-07239-w · Cited by 34
Photocatalytic Chemical Crosslinking for Profiling RNA–Protein Interactions in Living Cells
Luo, H., Tang, W., Liu, H., Zeng, X., Ngai, W. S. C., Gao, R., Li, H., Li, R., Zheng, H., Guo, J., et al. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202202008 · Cited by 33
TDP-43 high throughput screening analyses in neurodegeneration: Advantages and pitfalls
Buratti, E., Romano, M., & Baralle, F. E. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2013.03.001 · Cited by 32
CLIPing the brain: Studies of protein–RNA interactions important for neurodegenerative disorders
Modic, M., Ule, J., & Sibley, C. R. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2013.04.002 · Cited by 34
“By identifying themRNAs that are directly regulated by Nova proteins (Licatalosi et al., 2008; Ule et al., 2006), the Nova RNAmap enabled studies that revealed how specific mRNAs mediate the function of Nova proteins in the brain.”
InfluentialSelf-citation
Metadata
- Authors
- Licatalosi, D. D., Mele, A., Fak, J. J., Ule, J., Kayikci, M., Chi, S. W., Clark, T. A., Schweitzer, A. C., Blume, J. E., Wang, X., Darnell, J. C., & Darnell, R. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- MRC Laboratory of Molecular Biology (GB)
- Affymetrix (United States) (US)
- Rockefeller University (US)
- Corresponding author
- Darnell, Robert B.
- ORCID
- Venue
- Nature
- Published
- 2008-11
- Volume
- 456
- Issue
- 7221
- Pages
- 464-469
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2597294
- OpenAlex
- W2044117548
- Cited by
- 1,352
- References
- 51
- Citations by year
- 2026: 37 · 2025: 53 · 2024: 46 · 2023: 44 · 2022: 72 · 2021: 81 · 2020: 59 · 2019: 77 · 2018: 85 · 2017: 89 · 2016: 95 · 2015: 97 · 2014: 103 · 2013: 89 · 2012: 111
- FWCI
- 29.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R01NS040955, R01 NS34389, R01NS034389)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD040647)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- HITS-CLIP, RNA-protein interactions, alternative splicing, nova, alternative polyadenylation, 3' untranslated region, RNA binding sites, brain, neurons, splicing factors, genome-wide mapping
- MeSH terms
- Neuro-Oncological Ventral Antigen, Animals, Antigens, Neoplasm, Cell Line, Cross-Linking Reagents, Exons, Humans, Neurons, Organ Specificity, RNA, Messenger, RNA-Binding Proteins, Genome, Alternative Splicing, Neocortex, Genomics, Polyadenylation, Immunoprecipitation, Mice
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