IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15171-6.html
   My bibliography  Save this article

Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns

Author

Listed:
  • Alison D. Tang

    (University of California)

  • Cameron M. Soulette

    (University of California)

  • Marijke J. van Baren

    (University of California)

  • Kevyn Hart

    (University of California)

  • Eva Hrabeta-Robinson

    (University of California)

  • Catherine J. Wu

    (Dana-Farber Cancer Institute
    Broad Institiute of Harvard and MIT
    Brigham and Women’s Hospital, Harvard Medical School)

  • Angela N. Brooks

    (University of California)

Abstract

While splicing changes caused by somatic mutations in SF3B1 are known, identifying full-length isoform changes may better elucidate the functional consequences of these mutations. We report nanopore sequencing of full-length cDNA from CLL samples with and without SF3B1 mutation, as well as normal B cell samples, giving a total of 149 million pass reads. We present FLAIR (Full-Length Alternative Isoform analysis of RNA), a computational workflow to identify high-confidence transcripts, perform differential splicing event analysis, and differential isoform analysis. Using nanopore reads, we demonstrate differential 3’ splice site changes associated with SF3B1 mutation, agreeing with previous studies. We also observe a strong downregulation of intron retention events associated with SF3B1 mutation. Full-length transcript analysis links multiple alternative splicing events together and allows for better estimates of the abundance of productive versus unproductive isoforms. Our work demonstrates the potential utility of nanopore sequencing for cancer and splicing research.

Suggested Citation

  • Alison D. Tang & Cameron M. Soulette & Marijke J. van Baren & Kevyn Hart & Eva Hrabeta-Robinson & Catherine J. Wu & Angela N. Brooks, 2020. "Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15171-6
    DOI: 10.1038/s41467-020-15171-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15171-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-15171-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Hanyong Jin & Ji-Hyun Yeom & Eunkyoung Shin & Yoonjie Ha & Haifeng Liu & Daeyoung Kim & Minju Joo & Yong-Hak Kim & Hak Kyun Kim & Minkyung Ryu & Hong-Man Kim & Jeongkyu Kim & Keun P. Kim & Yoonsoo Hah, 2024. "5′-tRNAGly(GCC) halves generated by IRE1α are linked to the ER stress response," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. 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.
    3. Sepideh Tavakoli & Mohammad Nabizadeh & Amr Makhamreh & Howard Gamper & Caroline A. McCormick & Neda K. Rezapour & Ya-Ming Hou & Meni Wanunu & Sara H. Rouhanifard, 2023. "Semi-quantitative detection of pseudouridine modifications and type I/II hypermodifications in human mRNAs using direct long-read sequencing," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Yaqi Su & Zhejian Yu & Siqian Jin & Zhipeng Ai & Ruihong Yuan & Xinyi Chen & Ziwei Xue & Yixin Guo & Di Chen & Hongqing Liang & Zuozhu Liu & Wanlu Liu, 2024. "Comprehensive assessment of mRNA isoform detection methods for long-read sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Yuchao Xia & Zijie Jin & Chengsheng Zhang & Linkun Ouyang & Yuhao Dong & Juan Li & Lvze Guo & Biyang Jing & Yang Shi & Susheng Miao & Ruibin Xi, 2023. "TAGET: a toolkit for analyzing full-length transcripts from long-read sequencing," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Kensuke Yamaguchi & Kazuyoshi Ishigaki & Akari Suzuki & Yumi Tsuchida & Haruka Tsuchiya & Shuji Sumitomo & Yasuo Nagafuchi & Fuyuki Miya & Tatsuhiko Tsunoda & Hirofumi Shoda & Keishi Fujio & Kazuhiko , 2022. "Splicing QTL analysis focusing on coding sequences reveals mechanisms for disease susceptibility loci," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Jun Inamo & Akari Suzuki & Mahoko Takahashi Ueda & Kensuke Yamaguchi & Hiroshi Nishida & Katsuya Suzuki & Yuko Kaneko & Tsutomu Takeuchi & Hiroaki Hatano & Kazuyoshi Ishigaki & Yasushi Ishihama & Kazu, 2024. "Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    8. Mario Ivanković & Jeremias N. Brand & Luca Pandolfini & Thomas Brown & Martin Pippel & Andrei Rozanski & Til Schubert & Markus A. Grohme & Sylke Winkler & Laura Robledillo & Meng Zhang & Azzurra Codin, 2024. "A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    9. Michal Kabza & Alexander Ritter & Ashley Byrne & Kostianna Sereti & Daniel Le & William Stephenson & Timothy Sterne-Weiler, 2024. "Accurate long-read transcript discovery and quantification at single-cell, pseudo-bulk and bulk resolution with Isosceles," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    10. Kenzui Taniue & Anzu Sugawara & Chao Zeng & Han Han & Xinyue Gao & Yuki Shimoura & Atsuko Nakanishi Ozeki & Rena Onoguchi-Mizutani & Masahide Seki & Yutaka Suzuki & Michiaki Hamada & Nobuyoshi Akimits, 2024. "The MTR4/hnRNPK complex surveils aberrant polyadenylated RNAs with multiple exons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15171-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.