MIR100 host gene-encoded lncRNAs regulate cell cycle by modulating the interaction between HuR and its target mRNAs

Qinyu Sun, Vidisha Tripathi, Je Hyun Yoon, Deepak K. Singh, Qinyu Hao, Kyung Won Min, Sylvia Davila, Richard W. Zealy, Xiao Ling Li, Maria Polycarpou-Schwarz, Elin Lehrmann, Yongqing Zhang, Kevin G. Becker, Susan M. Freier, Yuelin Zhu, Sven Diederichs, Supriya G. Prasanth, Ashish Lal, Myriam Gorospe, Kannanganattu V. Prasanth

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10405-10416
Number of pages12
JournalNucleic acids research
Volume46
Issue number19
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Sun, Q., Tripathi, V., Yoon, J. H., Singh, D. K., Hao, Q., Min, K. W., Davila, S., Zealy, R. W., Li, X. L., Polycarpou-Schwarz, M., Lehrmann, E., Zhang, Y., Becker, K. G., Freier, S. M., Zhu, Y., Diederichs, S., Prasanth, S. G., Lal, A., Gorospe, M., & Prasanth, K. V. (2018). MIR100 host gene-encoded lncRNAs regulate cell cycle by modulating the interaction between HuR and its target mRNAs. Nucleic acids research, 46(19), 10405-10416. https://doi.org/10.1093/nar/gky696