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
    1. Weinstein JN
    2. et al
    (2013) The Cancer Genome Atlas
    The National Cancer Institute (NCI) provides access to all individuals seeking information on www.cancer.gov, including individuals who are disabled. To provide this information, the NCI website complies with Section 508 of the Rehabilitation Act (as amended).
    1. Mathelier A
    2. et al
    (2016) The high-quality transcription factor binding profile database (JASPAR)
    The database is ready to be deployed quickly for genome-wide studies through the JASPAR API.
    1. Hunter S
    2. et al
    (2009) InterPro: protein sequence analysis & classification
    New SOAP-based Web Services have been added to complement the existing InterProScan Web Service. These allow users to programmatically retrieve InterPro entry data such as the abstract, integrated signature lists or GO terms. Users can download a range of clients from http://www.ebi.ac.uk/Tools/webservices/clients/dbfetch, including PERL, C#.NET and Java clients, to access this data.

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.

Reviewing Editor

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

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).

Version 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.

Metrics

  • 3,032
    views
  • 652
    downloads
  • 70
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.30433

Further reading

    1. Cancer Biology
    2. Genetics and Genomics
    Kevin Nuno, Armon Azizi ... Ravindra Majeti
    Research Article

    Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse samples with ATAC-seq. This analysis identified a relapse-specific chromatin accessibility signature for mutationally stable AML, suggesting that AML undergoes epigenetic evolution at relapse independent of mutational changes. Analysis of leukemia stem cell (LSC) chromatin changes at relapse indicated that this leukemic compartment underwent significantly less epigenetic evolution than non-LSCs, while epigenetic changes in non-LSCs reflected overall evolution of the bulk leukemia. Finally, we used single-cell ATAC-seq paired with mitochondrial sequencing (mtscATAC) to map clones from diagnosis into relapse along with their epigenetic features. We found that distinct mitochondrially-defined clones exhibit more similar chromatin accessibility at relapse relative to diagnosis, demonstrating convergent epigenetic evolution in relapsed AML. These results demonstrate that epigenetic evolution is a feature of relapsed AML and that convergent epigenetic evolution can occur following treatment with induction chemotherapy.

    1. Cancer Biology
    2. Cell Biology
    Ibtisam Ibtisam, Alexei F Kisselev
    Short Report

    Rapid recovery of proteasome activity may contribute to intrinsic and acquired resistance to FDA-approved proteasome inhibitors. Previous studies have demonstrated that the expression of proteasome genes in cells treated with sub-lethal concentrations of proteasome inhibitors is upregulated by the transcription factor Nrf1 (NFE2L1), which is activated by a DDI2 protease. Here, we demonstrate that the recovery of proteasome activity is DDI2-independent and occurs before transcription of proteasomal genes is upregulated but requires protein translation. Thus, mammalian cells possess an additional DDI2 and transcription-independent pathway for the rapid recovery of proteasome activity after proteasome inhibition.