LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1 mRNA stability in human cells
- University of Science and Technology of China, China
- 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
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Myc regulates gene expression in P493-6 cell lines which carry a Myc tet-off systemPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106916).
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The impact of lncRNA LAST knockdown on gene expression profile in HCT116 cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106917).
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Identification of CNBP binding mRNA and the binding sites/motifs in HCT116 cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106918).
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The Cancer Genome AtlasThe 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).
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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.
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InterPro: protein sequence analysis & classificationNew 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
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).
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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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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