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

MIR100 host gene-encoded lncRNAs regulate cell cycle by modulating the interaction between HuR and its target mRNAs.
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DOI:
10.1093/nar/gky696
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发表时间:
2018-11-02
影响因子:
14.9
通讯作者:
Prasanth KV
Prasanth KV
中科院分区:
生物学2区
文献类型:
--
作者:
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

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长链非编码RNA(lncRNA)调节重要的生物学过程,包括细胞增殖、分化和发育。lncRNA的一个亚类由于前miRNA加工而从微小RNA(miRNA)宿主基因(MIRHG)合成,并且被分类为miRNA-宿主基因lncRNA(lnc-miRHG)。目前,大多数lnc-miRHG的细胞功能还不清楚。我们证明了核富集的lnc-miRHG在细胞周期进程中的miRNA独立作用。MIR 100 HG产生剪接和稳定的lncRNA,其在细胞周期的G1期期间显示升高的水平。人类细胞中MIR 100 HG编码的lncRNA的消耗导致异常的细胞周期进展,而不改变MIR 100 HG内编码的miRNA的水平。值得注意的是,MIR 100 HG与HuR/ELAVL 1以及几种HuR靶mRNA相互作用。此外,MIR 100 HG耗尽的细胞显示HuR与其三种靶mRNA之间的相互作用降低,表明MIR 100 HG促进HuR与靶mRNA之间的相互作用。我们的研究发现了MIRHG编码的lncRNA在调节RNA结合蛋白活性中所起的新作用,从而强调了确定人类基因组中存在的数百种lnc-miRHG功能的重要性。
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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