lnc-Mir100HG promotes cell proliferation by modulating the interation between HuR and its target mRNAs

Long non-coding RNAs (lncRNAs) regulate vital biological processes, including cell proliferation, differentiation and development. A subclass of lncRNAs is synthesized from microRNA host genes (MIRHGs) due to pre-miRNA processing, and is categorized as miRNA-host gene lncRNAs (lnc-miRHGs). Presently, it is not clear whether lnc-miRHG perform additional functions. We demonstrate a miRNA-independent role for a nuclear-enriched lnc-miRHG in cell cycle progression. MIR100HG produces spliced and stable lncRNAs (lnc-MIR100HG) that display elevated levels during the G1 phase of the cell cycle. Depletion of lnc-MIR100HG in human cells results in aberrant cell cycle progression with out altering the levels of miRNA encoded within MIR100HG. Notably, lnc-MIR100HG interacts with the HuR/Elav as well as with several of HuR-target mRNAs. Further, lnc-MIR100HG-depleted cells show reduced interaction between HuR and its target mRNAs, indicating that lnc-MIR100HG facilitates interaction between HuR and target mRNAs. Our studies have unearthed novel roles played by miRHG-encoded lncRNAs in regulating RNA binding protein activity, thereby underscoring the importance of determining the function of several hundreds of miRHG lncRNAs that are present in human genome.

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Sun Q, Tripathi V, Yoon JH, Singh DK, Hao Q, Min KW, Davila S, Zealy RW, Li XL, Polycarpou-Schwarz M, Lehrmann E, Zhang Y, Becker KG, Freier SM, Zhu Y, Diederichs S, Prasanth SG, Lal A, Gorospe M, Prasanth KV