Journal
NUCLEIC ACIDS RESEARCH
Volume 46, Issue 19, Pages 10405-10416Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky696
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Funding
- National Institute of Health [1RO1GM088252, 1RO1GM099669]
- American Cancer Society [RSG-11-174-01-RMC]
- National Science Foundation [1243372, EAGER 1723008]
- National Institute on Aging intramural Research Program, NIH [Z01-AG000511]
- Medical University of South Carolina
- Hollings Cancer Center
- National Institute on Cancer Intramural Research Program, NIH
- UIUC
- NATIONAL CANCER INSTITUTE [ZIABC011646] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM125196] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [ZIAAG000511, ZICAG000616] Funding Source: NIH RePORTER
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Long non-coding RNAs (lncRNAs) regulate vital biological processes, including cell proliferation, differentiation and development. A subclass of lncRNAs is synthesized from microRNA (miRNA) host genes (MIRHGs) due to pre-miRNA processing, and are categorized as miRNA-host gene lncRNAs (lnc-miRHGs). Presently, the cellular function of most lnc-miRHGs is not well understood. We demonstrate a miRNA-independent role for a nuclear-enriched lnc-miRHG in cell cycle progression. MIR100HG produces spliced and stable lncRNAs that display elevated levels during the G1 phase of the cell cycle. Depletion of MIR100HG-encoded lncRNAs in human cells results in aberrant cell cycle progression without altering the levels of miRNA encoded within MIR100HG. Notably, MIR100HG interacts with HuR/ELAVL1 as well as with several HuR-target mRNAs. Further, MIR100HG-depleted cells show reduced interaction between HuR and three of its target mRNAs, indicating that MIR100HG facilitates interaction between HuR and target mRNAs. Our studies have unearthed novel roles played by a MIRHG-encoded lncRNA in regulating RNA binding protein activity, thereby underscoring the importance of determining the function of several hundreds of lnc-miRHGs that are present in human genome.
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