LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1 mRNA stability in human cells

  1. Limian Cao
  2. Pengfei Zhang
  3. Jinming Li
  4. Mian Wu  Is a corresponding author
  1. University of Science and Technology of China, China
  2. Henan Provincial People's Hospital, China

Abstract

Cyclin D1 is a critical regulator of cell cycle progression and works at the G1 to S-phase transition. Here, we report the isolation and characterization of the novel c-Myc-regulated lncRNA LAST (LncRNA-Assisted Stabilization of Transcripts), which acts as a CCND1 mRNA stabilizer. Mechanistically, LAST was shown to cooperate with CNBP to bind to the 5′UTR of CCND1 mRNA to protect against possible nuclease targeting. In addition, data from CNBP RIP-seq and LAST RNA-seq showed that CCND1 mRNA might not be the only target of LAST and CNBP; three additional mRNAs were shown to be post-transcriptional targets of LAST and CNBP. In a xenograft model, depletion of LAST diminished and ectopic expression of LAST induced tumor formation, which are suggestive of its oncogenic function. We thus report a previously unknown lncRNA involved in the fine-tuned regulation of CCND1 mRNA stability, without which CCND1 exhibits, at most, partial expression.

Data availability

The following data sets were generated
The following previously published data sets were used
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Article and author information

Author details

  1. Limian Cao

    School of Life Sciences, University of Science and Technology of China, Hefei, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Pengfei Zhang

    School of Life Sciences, University of Science and Technology of China, Hefei, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Jinming Li

    Translational Research Institute, Henan Provincial People's Hospital, Zhengzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Mian Wu

    School of Life Sciences, University of Science and Technology of China, Hefei, China
    For correspondence
    wumian@ustc.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2714-0500

Funding

Ministry of Science and Technology of the People's Republic of China (2016YFC1302302)

  • Mian Wu

National Natural Science Foundation of China (81430065)

  • Mian Wu

National Natural Science Foundation of China (31371388)

  • Mian Wu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Studies on animals in this paper were conducted with approval from the Animal Research Ethics Committee of the University of Science and Technology of China (Permit Number: USTCACUC1701003).

Reviewing Editor

  1. Igor Ulitsky, The Weizmann Institute of Science, Israel

Publication history

  1. Received: July 14, 2017
  2. Accepted: December 2, 2017
  3. Accepted Manuscript published: December 4, 2017 (version 1)
  4. Version of Record published: December 21, 2017 (version 2)

Copyright

© 2017, Cao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Limian Cao
  2. Pengfei Zhang
  3. Jinming Li
  4. Mian Wu
(2017)
LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1 mRNA stability in human cells
eLife 6:e30433.
https://doi.org/10.7554/eLife.30433

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