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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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“Many variations (HITS-CLIP, PAR-CLIP, iCLIP) have been described 9–12 , all of which follow the same basic strategy: crosslinking of protein-RNA interactions, digestion or shearing of the RNA to smaller fragments, immunoprecipitation of the targeted protein (and associated RNA) using a…”
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Toombs, J. A., Sytnikova, Y. A., Chirn, G., Ang, I. W. S., Lau, N. C., & Blower, M. D. (2016) · RNA · doi:10.1261/rna.058859.116 · Cited by 16
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Self-citationTransferrin receptor mRNA interactions contributing to iron homeostasis
Rupani, D. N., & Connell, G. J. (2016) · RNA · doi:10.1261/rna.056184.116 · Cited by 16
“Optimization and adaptation of the RNA-CLIP methodology to IRP-1 The RNA-CLIP libraries were prepared similarly to those described earlier (Licatalosi et al. 2008; Wang et al. 2009; Konig et al. 2011).”
MethodDO-RIP-seq to quantify RNA binding sites transcriptome-wide
Nicholson, C. O., Friedersdorf, M. B., Bisogno, L. S., & Keene, J. D. (2016) · Methods · doi:10.1016/j.ymeth.2016.11.004 · Cited by 16
Methods to study the RNA-protein interactions
Popova, V. V., Куршакова, М. М., & Kopytova, D. V. (2015) · Molecular Biology · doi:10.1134/s0026893315020107 · Cited by 19
Jeong, J., Yoo, H. J., An, J., & Jeong-Yu, S. (2025) · Molecules and Cells · doi:10.1016/j.mocell.2025.100237 · Cited by 15
“A high-throughput sequencing cross-linking immunoprecipitation (HITS-CLIP) study mapped over 16,000 NOVA2-binding sites in the mouse genome, identifying its role in synaptic proteins and axon guidance through genes such as Dcc , Robo2 , Slit2 , and Epha5 (Licatalosi et al., 2008; Ule et al., 2003).”
Jiang, Z., Xiao, S.-R., & Liu, R. (2021) · Briefings in Bioinformatics · doi:10.1093/bib/bbab411 · Cited by 15
SRSF2 is required for mRNA splicing during spermatogenesis
Lei, W., Du, Z., Meng, T., Su, R., Li, Y., Liu, W., Sun, S., Liu, M., Hou, Y., Zhang, C., et al. (2023) · BMC Biology · doi:10.1186/s12915-023-01736-6 · Cited by 16
HuR's role in gemcitabine efficacy: an exception or opportunity?
Brody, J. R., & Gonye, G. E. (2010) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.62 · Cited by 15
Kim, K.-K., Ham, J., & Chi, S. W. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt296 · Cited by 15
“Recently, by applying cross-linking immunoprecipitation method (CLIP) coupled with high-throughput sequencing (HITS) (Licatalosi, 2008) to a protein called Argonaute (Ago HITS-CLIP), all miRNA-binding regions in target mRNAs were experimentally mapped in high resolution (Chi et al., 2009).”
MethodSelf-citationEfficiency of the miRNA–mRNA Interaction Prediction Programs
Plotnikova, O., & Skoblov, M. Y. (2018) · Molecular Biology · doi:10.1134/s0026893318020103 · Cited by 15
“Importantly, Starbase v.2.0 contains only predictions supported by human CLIP-Seq data (HITS-CLIP, PAR-CLIP, iCLIP and CLASH).”
MethodInfluentialGene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells
Belloni, E., Matteo, A. D., Pradella, D., Vacca, M., Wyatt, C. D. R., Alfieri, R. R., Maffia, A., Sabbioneda, S., & Ghigna, C. (2019) · Cells · doi:10.3390/cells8121498 · Cited by 15
“The position of Nova2 binding sites predicts the outcome of the splicing reaction following the rule that Nova2 promotes exon skipping when bound to the exonic or upstream intronic YCAY clusters, while it stimulates exon inclusion when interacting with downstream intronic motifs [25,32].”
BackgroundInfluentialKalathiya, U., Padariya, M., Faktor, J., Coyaud, É., Alfaro, J. A., Fåhræus, R., Hupp, T. R., & Goodlett, D. R. (2021) · Biomolecules · doi:10.3390/biom11030382 · Cited by 14
“Techniques in which the UV cross-linking is followed by the protein purification and bound RNAs can be identified are widely termed cross-linking immunoprecipitation (CLIP) methods [164], along with those using the high-throughput sequencing (HTS) forming the CLIP-seq family of methods [165].”
MethodGuo, Y., & Lei, X. (2022) · Methods · doi:10.1016/j.ymeth.2022.09.003 · Cited by 15
Transcriptional activators enhance polyadenylation of mRNA precursors
Nagaike, T., & Manley, J. L. (2011) · RNA Biology · doi:10.4161/rna.8.6.17210 · Cited by 15
Guardian of Genetic Messenger-RNA-Binding Proteins
Anji, A., & Kumari, M. (2016) · Biomolecules · doi:10.3390/biom6010004 · Cited by 15
“Some of the high-throughput assays currently employed by RNA biologists to study post-transcriptional regulation are CLIP, HITS-CLIP, PAR-CLIP and iCLIP [17].”
MethodInfluentialRegulation of Tissue-Specific Alternative Splicing: C. elegans as a Model System
Gracida, X., Norris, A. D., & Calarco, J. A. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-29073-7_10 · Cited by 15
Deng, L., Liu, Y., Shi, Y., & Liu, H. (2019) · IEEE International Conference on Bioinformatics and Biomedicine (BIBM) · doi:10.1109/bibm47256.2019.8983345 · Cited by 15
“Recently, high-throughput technique, such as the crosslinking immunoprecipitation coupled with high-through-put sequencing (CLIP-seq) protocols, has greatly advanced the genome-wide studies of RNA-protein interactions [3–5].”
BackgroundChaudhuri, A., Das, S., & Das, B. (2020) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1591 · Cited by 16
“…specificity, a more informative and accurate UV-crosslinking and immunoprecipitation (CLIP) linked to high-throughput sequencing (HITS-CLIP or CLIP-Seq) was developed (Hafner et al., 2010; König, Zarnack, Luscombe, & Ule, 2012; Licatalosi et al., 2008; Ule et al., 2003; Van Nostrand et al., 2016).”
BackgroundPRIME-3D2D is a 3D2D model to predict binding sites of protein–RNA interaction
Xie, J., Zheng, J., Hong, X., Tong, X., & Liu, S. (2020) · Communications Biology · doi:10.1038/s42003-020-1114-y · Cited by 15
Zooming in on protein–RNA interactions: a multi-level workflow to identify interaction partners
Colantoni, A., Rupert, J., Vandelli, A., Tartaglia, G. G., & Zacco, E. (2020) · Biochemical Society Transactions · doi:10.1042/bst20191059 · Cited by 16
Kloetgen, A., Münch, P. C., Borkhardt, A., Hoell, J. I., & McHardy, A. C. (2014) · Briefings in Functional Genomics · doi:10.1093/bfgp/elu020 · Cited by 14
“Ultraviolet (UV) CLIP methods [22, 31–33]”
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“In 2008, to accurately illustrate the RNA-binding sites of an any given RBP on a large scale, Licatalosi and colleagues introduced the next-generation sequencing (NGS) technology to CLIP method, and invented high-throughput sequencing of CLIP cDNA library (HITS-CLIP; Licatalosi et al., 2008).”
BackgroundMethodGene Duplication and Alternative Splicing as Evolutionary Drivers of Proteome Specialization
Mantica, F., & Irimia, M. (2025) · BioEssays · doi:10.1002/bies.202400202 · Cited by 13
Next generation quantitative genetics in plants
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“Examples of these phenotypes are protein–RNA interactions (Licatalosi et al., 2008; Hafner et al., 2010), translation rates (Ingolia et al., 2009; Ingolia, 2010), transcription rates (Core et al., 2008; Churchman and Weissman, 2011), protein–DNA interactions (Albert et al., 2007; Barski et al.,…”
BackgroundLuo, H., Li, J., Chia, B. K. H., Robson, P., & Nagarajan, N. (2014) · Genome biology · doi:10.1186/s13059-014-0527-7 · Cited by 14
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Bieniasz, P. D., & Kutluay, S. B. (2018) · Retrovirology · doi:10.1186/s12977-018-0417-2 · Cited by 14
“The inception of the original CLIP protocol [7, 8] and its subsequent coupling to next-generation sequencing [9] has revolutionized the study of protein–RNA interactions.”
BackgroundMethodA Pipeline for Analyzing eCLIP and iCLIP Data with Htseq-clip and DEWSeq
Sahadevan, S., Sekaran, T., & Schwarzl, T. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1851-6_10 · Cited by 14
Biochemical Approaches Including the Design and Use of Strains Expressing Epitope-Tagged Proteins
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Analysis of HIV-1 Gag-RNA Interactions in Cells and Virions by CLIP-seq
Kutluay, S. B., & Bieniasz, P. D. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3046-3_8 · Cited by 14
“To identify the RNA molecules directly bound by Gag in physiological settings, we have recently applied CLIP-seq methodologies (15,16) to various stages of particle genesis (17).”
MethodLema, I., Amazit, L., Lamribet, K., Fagart, J., Blanchard, A., Lombès, M., Cherradi, N., & Viengchareun, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-04838-8 · Cited by 17
Expanding the map of protein-RNA interaction sites via cell fusion followed by PAR-CLIP
Hinze, F., Drewe-Boß, P., Milek, M., Ohler, U., Landthaler, M., & Gotthardt, M. (2017) · RNA Biology · doi:10.1080/15476286.2017.1384120 · Cited by 14
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Chen, S., Li, C., Jia, X., & Lai, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153834 · Cited by 14
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Self-citationMetabolite sensing in eukaryotic mRNA biology
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RNA Processing: Redrawing the Map of Charted Territory
Corrionero, A., & Valcárcel, J. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.12.004 · Cited by 15
“RNA maps have been reported for the tissue-specific splicing regulators Nova and Fox2 (Ule et al., 2006; Licatalosi et al., 2008; Yeo et al., 2009).”
BackgroundMethodStem Cell Ribonomics: RNA-Binding Proteins and Gene Networks in Stem Cell Differentiation
Shigunov, P., & Dallagiovanna, B. (2015) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2015.00074 · Cited by 14
Dynamic U2AF cycling defines two phases of cotranscriptional pre-mRNA splicing
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Cao, H., Wang, Y., Zhang, N., Xia, S., Tian, P., Li, L., Du, J., & Du, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.866820 · Cited by 16
Haroon, M., Afzal, R., Zafar, M. M., Zhang, H., & Li, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23115923 · Cited by 13
“PAR-CLIP, HITS-CLIP Efficient, RBPs can be identified at the 3′ end of RNA, highly specific UV cross-linking does not bind the RNA proteins well which can lead to a high number of false positives, crosslinked nucleotides are bypassed by reverse transcriptase, it is a laborious and time-consuming protocol [24,25]”
BackgroundCRBSP:Prediction of CircRNA-RBP Binding Sites Based on Multimodal Intermediate Fusion
Liu, N., Zhang, Z., Wu, Y., Wang, Y., & Liang, Y. (2023) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2023.3272400 · Cited by 13
“CLIP(cross-linkingandimmuno-precipitation)hasbeensuccessfullydevelopedintoCLIP-seq toshowinvivobindingsitesofCircRNA-RBP[19],[20].”
Deep sequencing of coding and non-coding RNA in the CNS
van der Brug, M., Nalls, M. A., & Cookson, M. (2010) · Brain Research · doi:10.1016/j.brainres.2010.03.039 · Cited by 13
“The ability of deep sequencing to provide quantitation of the numbers of tags recovered was important in this study as it allowed Licatalosi et al to show that large numbers of Nova tags were recovered in the 3’ UTR of genes, which then lead to the biological insight that Nova regulates alternative polyadenylation in…”
MethodAssessing Computational Steps for CLIP-Seq Data Analysis
Liu, Q., Zhong, X. Y., Madison, B., Rustgi, A. K., & Shyr, Y. (2015) · BioMed Research International · doi:10.1155/2015/196082 · Cited by 13
“For example, in contrast to only 34 Nova-bound transcripts detected in the original CLIP experiments, the first application of HITS-CLIP identified 2,481 Nova-bound RNAs [12].”
MethodResultGenome-Wide Analyses of Circadian Systems
Reddy, A. B. (2013) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25950-0_16 · Cited by 13
Protein-mRNA interactome capture: cartography of the mRNP landscape
Ryder, S. (2016) · F1000Research · doi:10.12688/f1000research.9404.1 · Cited by 14
“This will require the development of new technology, or the application of existing single gene methods such as CLIP and PAR-CLIP at much higher throughput 35,36,84,91 , which will require a dramatic increase in resources and effort.”
MethodLong, M. J. C., Zhao, Y., & Aye, Y. (2020) · RSC Chemical Biology · doi:10.1039/d0cb00041h · Cited by 13
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Rohani, N., Moughari, F. A., & Eslahchi, C. (2021) · PeerJ · doi:10.7717/peerj.10505 · Cited by 13
Jouravleva, K., Vega‐Badillo, J., & Zamore, P. D. (2022) · Cell Reports Methods · doi:10.1016/j.crmeth.2022.100185 · Cited by 13
“…crosslinking and immunoprecipitation yield comprehensive lists of RNA-binding motifs but do not enable quantitative assessment of binding affinities (Licatalosi et al., 2008; Ko¨nig et al., 2010; Zhao et al., 2010; Danan et al., 2016; Sugimoto et al., 2012; Kishore et al., 2011; Campbell and…”
BackgroundNext-generation sequencing: A new avenue to understand viral RNA–protein interactions
Zhou, Y., Sotcheff, S. L., & Routh, A. L. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101924 · Cited by 13
“CoupledwithNGS, a number of high-throughput platforms such as high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) (22), PhotoActivatableRibonucleoside–Enhanced Crosslinking and ImmunoPrecipitation (PAR-CLIP) (23), and viral PhotoActivatableRibonucleoside CrossLinking (vPAR-CL) (2…”
InfluentialMolecular characterization of Plasmodium falciparum Bruno/CELF RNA binding proteins
Wongsombat, C., Aroonsri, A., Kamchonwongpaisan, S., Morgan, H. P., Walkinshaw, M. D., Yuthavong, Y., & Shaw, P. J. (2014) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2014.10.005 · Cited by 13
CLIPick: a sensitive peak caller for expression-based deconvolution of HITS-CLIP signals
Park, S., Ahn, S. H., Cho, E. S., Cho, Y. K., Jang, E.-S., & Chi, S. W. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky917 · Cited by 13
“The expected fragment number of transcript i (EFi ), which accounts for its length and abundance, was estimated by assigning NPi as the number for each transcript and multiplying it by the number of fragments per transcript, estimated by dividing the length of transcript i (Li ) with the observed average size of fragm…”
BackgroundMethodSelf-citationIdentifying and validating small molecules interacting with RNA (SMIRNAs)
Disney, M. D., Velagapudi, S. P., Li, Y., Costales, M. G., & Childs‐Disney, J. L. (2019) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2019.04.027 · Cited by 13
“The Chem-CLIP approach is a chemical method of cross-linking that is operationally similar to the technique described by Darnell and co-workers to define protein-RNA binding sites via Cross-linking and immunoprecipitation (CLIP) (Licatalosi et al., 2008; Ule et al., 2003).”
MethodmRNA isoform balance in neuronal development and disease
LaForce, G. R., Philippidou, P., & Schaffer, A. E. (2022) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1762 · Cited by 15
“In contrast, miRNA-mediated repression is a mechanism to regulate the expression of most cell type-specific isoforms (Ji & Tian, 2009; Licatalosi et al., 2008; Miura et al., 2013; Nam et al., 2014; Rodrigues et al., 2016).”
BackgroundInfluentialTavanez, J. P., & Valcárcel, J. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.234 · Cited by 13
Analysis of base-pairing probabilities of RNA molecules involved in protein–RNA interactions
Iwakiri, J., Kameda, T., Asai, K., & Hamada, M. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt453 · Cited by 13
Decoding Abnormal Splicing Code in Human Diseases
Ohno, K. (2015) · Journal of Investigative Genomics · doi:10.15406/jig.2015.02.00016 · Cited by 12
Методы исследования взаимодействия белков с РНК
Попова, В. В., Куршакова, М. М., & Kopytova, D. V. (2015) · Molecular Biology · doi:10.7868/s0026898415020111 · Cited by 13
Decoding RNA–Protein Interactions: Methodological Advances and Emerging Challenges
Yi, W., & Yan, J. (2025) · Advanced Genetics · doi:10.1002/ggn2.202500011 · Cited by 12
Co-profiling of in situ RNA-protein interactions and transcriptome in single cells and tissues
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“Next, we characterized the genomic distribution of edit clusters from five MAPIT-seq libraries above to capture RBP-specific binding patterns (Supplementary Tables 13–17).”
InfluentialHan, Y. Y., Guo, X., Zhang, T., Wang, J., & Ye, K. (2021) · RNA · doi:10.1261/rna.078896.121 · Cited by 12
“Purification of crosslinked RNP and construction of sequencing library The crosslinked RNA was purified and cloned as previously described (Granneman et al. 2009; Lin et al. 2013).”
MethodIdentification of RNA-Binding Protein Targets with HyperTRIBE in Saccharomyces cerevisiae
Piao, W., Li, C., Sun, P., Yang, M., Ding, Y., Song, W., Jia, Y., Yu, L., Lu, Y., & Jin, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24109033 · Cited by 13
“Of the above, HITS-CLIP (CLIP-seq) has been widely used as a powerful method for detecting RBP-binding sites on RNA at a single-nucleotide resolution [9].”
Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq
Patel, S., Sexton, A. N., Strine, M. S., Wilen, C. B., Simon, M. D., & Pyle, A. M. (2023) · Nature Communications · doi:10.1038/s41467-023-38623-1 · Cited by 11
Post-transcriptional mechanisms controlling neurogenesis and direct neuronal reprogramming
Papadimitriou, E., & Thomaidou, D. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.390976 · Cited by 14
“…metabolism, such as alternative splicing (AS) (Makeyev et al., 2007; Licatalosi et al., 2012; Li et al., 2015b), polyadenylation (Zhu et al., 2006; Licatalosi et al., 2008; Sena et al., 2021), RNA editing (Merkurjev et al., 2018; Chen et al., 2019), stability (Lou et al., 2014; Dai et al., 2015;…”
BackgroundPost-transcriptional regulation of the transcriptional apparatus in neuronal development
Nazim, M. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1483901 · Cited by 12
Chen, L. (2012) · Statistics in Biosciences · doi:10.1007/s12561-012-9064-7 · Cited by 14
“ping unique sequence tags were defined as clusters [31, 42].”
BackgroundWeyn‐Vanhentenryck, S. M., & Zhang, C. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3591-8_17 · Cited by 12
mRNA interactome capture in mammalian cells
Kastelić, N., & Landthaler, M. (2017) · Methods · doi:10.1016/j.ymeth.2017.07.006 · Cited by 13
Sibley, C. R. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7213-5_29 · Cited by 12
The Genetic Control of Stoichiometry Underlying Autism
Darnell, R. B. (2020) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-100119-024851 · Cited by 12
“Subsequent unbiased, genome-wide approaches afforded by CLIP, including pioneering exon-junction splicing microarrays (Ule et al. 2005), HITS-CLIP (Licatalosi et al. 2008), and bioinformatic analyses (Ule et al. 2006, Zhang et al. 2010), identified a robust set of ~800 target alternative exons (Ule et al. 2018).”
InfluentialSelf-citationRNA-Binding Protein Immunopurification-Microarray (RIP-Chip) Analysis to Profile Localized RNAs
Galgano, A., & Gerber, A. P. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-005-8_23 · Cited by 12
Human microRNA target identification by RRSM
Hsieh, W. J., & Wang, H. (2011) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2011.06.022 · Cited by 12
Spicuglia, S., Maqbool, M. A., Puthier, D., & Andrau, J. (2013) · Methods · doi:10.1016/j.ymeth.2013.04.003 · Cited by 17
Grozdanov, P. N., & MacDonald, C. C. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-971-0_17 · Cited by 12
“The approach that combines ultraviolet cross-linking and immunoprecipitation (CLIP, [8]) with high-throughput sequencing of cDNAs generated from the bound RNA fragments (HITS-CLIP, [9]) is ideal for global analysis of these protein– RNA interactions to reveal functional insights [10].”
BackgroundMapping transcriptome‐wide protein‐RNA interactions to elucidate RNA regulatory programs
Hannigan, M. M., Zagore, L. L., & Licatalosi, D. D. (2018) · Quantitative Biology · doi:10.1007/s40484-018-0145-6 · Cited by 13
“In comparison, a 2008 study coupling CLIP with high-throughput sequencing [26] generated ~168,000 CLIP reads and revealed thousands of biologically reproducible NOVA-RNA interactions across the brain transcriptome.”
Self-citationPeroxiredoxin 1 post-transcriptionally regulates snoRNA expression
Kim, E.-K., Lee, S. Y., Kim, Y., Ahn, S., & Jang, H. H. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.05.030 · Cited by 13
Lessons from single cell sequencing in CNS cell specification and function
Li, Z., Tyler, W. A., & Haydar, T. F. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.05.043 · Cited by 14
“The activity of microRNAs (miRNA) can also influence post transcriptional expression, and methods like CLIP-seq (53) can now map miRNA expression in single cells.”
MethodChen, F., Zhou, Y., Qi, Y. B., Khivansara, V., Li, H., Chun, S. Y., Kim, J. K., Fu, X., & Jin, Y. (2015) · Genes & Development · doi:10.1101/gad.266650.115 · Cited by 12
“3 ′ UTRome profiling and Pol II occupancy assay 3 ′ UTR libraries were constructed and sequenced as described (Mangone et al. 2010).”
Noncoding RNAs orchestrating the central dogma
Lozano‐Villada, S., & Puthanveettil, S. V. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110933 · Cited by 13
“These mechanistic gaps point to the need for subcellular CLIP-seq, cryo-ET of ribonucleoprotein particles, and cross-linking mass spectrometry to map how ncRNAs physically interface with the translational apparatus and kinase domains.”
UV-RNA Immunoprecipitation (UV-RIP) Protocol in Neurons
Schaukowitch, K., Joo, J., & Kim, T.-K. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-4035-6_4 · Cited by 11
CLIP and complementary methods
(2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00023-4 · Cited by 15
The edited transcriptome: novel high throughput approaches to detect nucleotide deamination
Silberberg, G., & Öhman, M. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2011.04.009 · Cited by 11
Li, B., Ngo, S., Wu, W., Xu, H., Xie, Z., Li, Q., & Pan, Z. (2014) · Gene · doi:10.1016/j.gene.2014.08.028 · Cited by 11
Besenyei, T., Kádár, A., Tryniszewska, B., Kurkó, J., Rauch, T. A., Glant, T. T., Mikecz, K., & Szekanecz, Z. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/284751 · Cited by 11
“Alternatively, for example, if miRNA-related sequences are expected, the high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) with antibodies against the RNA-binding protein Argonaut (Ago HITSCLIP) [134–138] may offer another solution.”
BackgroundCLIP-Seq in Bacteria: Global Recognition Patterns of Bacterial RNA-Binding Proteins
Andresen, L., & Holmqvist, E. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2018.08.008 · Cited by 11
Sindhu, K. J., Venkatesan, N., & Karunagaran, D. (2021) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2021.0087 · Cited by 11
“…(CLIP), affinity pull-down, degradome sequencing, or bioinformatics prediction (German et al., 2008; Hafner et al., 2010; Helwak et al., 2013; Keene et al., 2006; Kern et al., 2019; Licatalosi et al., 2008; Lu and Leslie, 2016; Moore et al., 2015; Willmann et al., 2014; Yoon et al., 2012).”
Xu, J., Wang, D., Ma, H., Zhai, X., Huo, Y., Ren, Y., Li, W., Chang, L., Lu, D., Guo, Y., et al. (2022) · Blood Science · doi:10.1097/bs9.0000000000000122 · Cited by 11
Self-citationWang, Z., & Lei, X. (2022) · Methods · doi:10.1016/j.ymeth.2022.06.014 · Cited by 11
RNA-Binding Proteins: A Role in Neurotoxicity?
Ocharán-Mercado, A., Loaeza-Loaeza, J., Castro-Coronel, Y., Acosta-Saavedra, L. C., Hernández-Kelly, L. C., Hernández-Sotelo, D., & Ortega, A. (2023) · Neurotoxicity research · doi:10.1007/s12640-023-00669-w · Cited by 9
“Loss of Nova proteins, as a result of an autoimmune paraneoplastic neurological disorder, manifests itself in neurological symptoms of excess motor movements (paraneoplastic myoclonic opsoclonus ataxia, POMA), on other hand, TPD-43 has been involved in ALS pathology (Buckanovich et al. 1993).”
BackgroundInfluential
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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