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HITS-CLIP yields genome-wide insights into brain alternative RNA processing

Author

Listed:
  • Donny D. Licatalosi

    (Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute,)

  • Aldo Mele

    (Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute,)

  • John J. Fak

    (Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute,)

  • Jernej Ule

    (MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK)

  • Melis Kayikci

    (MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK)

  • Sung Wook Chi

    (Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute,)

  • Tyson A. Clark

    (Expression Research, Affymetrix, Inc., Santa Clara, California 95051, USA)

  • Anthony C. Schweitzer

    (Expression Research, Affymetrix, Inc., Santa Clara, California 95051, USA)

  • John E. Blume

    (Expression Research, Affymetrix, Inc., Santa Clara, California 95051, USA)

  • Xuning Wang

    (Biocomputing, Information Technology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA)

  • Jennifer C. Darnell

    (Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute,)

  • Robert B. Darnell

    (Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute,)

Abstract

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.

Suggested Citation

  • Donny D. Licatalosi & Aldo Mele & John J. Fak & Jernej Ule & Melis Kayikci & Sung Wook Chi & Tyson A. Clark & Anthony C. Schweitzer & John E. Blume & Xuning Wang & Jennifer C. Darnell & Robert B. Darn, 2008. "HITS-CLIP yields genome-wide insights into brain alternative RNA processing," Nature, Nature, vol. 456(7221), pages 464-469, November.
    • Handle: RePEc:nat:nature:v:456:y:2008:i:7221:d:10.1038_nature07488
    DOI: 10.1038/nature07488
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    Cited by:

    1. Raphaël Dos Reis & Etienne Kornobis & Alyssa Pereira & Frederic Tores & Judit Carrasco & Candice Gautier & Céline Jahannault-Talignani & Patrick Nitschké & Christian Muchardt & Andreas Schlosser & Han, 2022. "Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Areum Han & Peter Stoilov & Anthony J Linares & Yu Zhou & Xiang-Dong Fu & Douglas L Black, 2014. "De Novo Prediction of PTBP1 Binding and Splicing Targets Reveals Unexpected Features of Its RNA Recognition and Function," PLOS Computational Biology, Public Library of Science, vol. 10(1), pages 1-18, January.
    3. Haoran Zhu & Yuning Yang & Yunhe Wang & Fuzhou Wang & Yujian Huang & Yi Chang & Ka-chun Wong & Xiangtao Li, 2023. "Dynamic characterization and interpretation for protein-RNA interactions across diverse cellular conditions using HDRNet," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    4. Tao Wang & Beibei Chen & MinSoo Kim & Yang Xie & Guanghua Xiao, 2014. "A Model-Based Approach to Identify Binding Sites in CLIP-Seq Data," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-11, April.
    5. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Huijuan Feng & Xiang-Jun Lu & Suvrajit Maji & Linxi Liu & Dmytro Ustianenko & Noam D. Rudnick & Chaolin Zhang, 2024. "Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Elizabeth A. Werren & Geneva R. LaForce & Anshika Srivastava & Delia R. Perillo & Shaokun Li & Katherine Johnson & Safa Baris & Brandon Berger & Samantha L. Regan & Christian D. Pfennig & Sonja Munnik, 2024. "TREX tetramer disruption alters RNA processing necessary for corticogenesis in THOC6 Intellectual Disability Syndrome," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    8. Xiangbin Ruan & Kaining Hu & Xiaochang Zhang, 2023. "PIE-seq: identifying RNA-binding protein targets by dual RNA-deaminase editing and sequencing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Shivali Patel & Alec N. Sexton & Madison S. Strine & Craig B. Wilen & Matthew D. Simon & Anna Marie Pyle, 2023. "Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    10. Liang-Cui Chu & Pedro Arede & Wei Li & Erika C. Urdaneta & Ivayla Ivanova & Stuart W. McKellar & Jimi C. Wills & Theresa Fröhlich & Alexander Kriegsheim & Benedikt M. Beckmann & Sander Granneman, 2022. "The RNA-bound proteome of MRSA reveals post-transcriptional roles for helix-turn-helix DNA-binding and Rossmann-fold proteins," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Zhiping Zhang & Bongmin Bae & Winston H. Cuddleston & Pedro Miura, 2023. "Coordination of alternative splicing and alternative polyadenylation revealed by targeted long read sequencing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. André Corvelo & Martina Hallegger & Christopher W J Smith & Eduardo Eyras, 2010. "Genome-Wide Association between Branch Point Properties and Alternative Splicing," PLOS Computational Biology, Public Library of Science, vol. 6(11), pages 1-13, November.

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