In-depth characterization of the microRNA transcriptome in a leukemia progression model

Kuchenbauer, Florian; Morin, Ryan D.; Argiropoulos, Bob; Petriv, Oleh I.; Griffith, Malachi; Heuser, Michael; Yung, Eric; Piper, Jessica; Delaney, Allen; Prabhu, Anna‐Liisa; Zhao, Yongjun; McDonald, Helen; Zeng, Thomas; Hirst, Martin; Hansen, Carl L.; Marra, Marco A.; Humphries, R. Keith

doi:10.1101/gr.077578.108

Cited by 164 publications

(161 citation statements)

References 64 publications

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“…In-depth miRNA profiling by deep sequencing with high-resolution views of expressed miRNAs over a wide dynamic range of expression levels has already been realized in several kinds of tissues and cell types, including human embryonic stem cells (25), human B cells (26), cell types during mouse lymphopoiesis (17), human renal cell carcinoma (27), and mouse leukemia (28). The study that revealed dynamic miRNomes during lymphopoiesis selected mouse adherent lymphokine-activated NK cells (ALAK, NK cells) as a mouse NK cell substitute to get the mouse NK cell miRNome (17), which may affect the biological and physiological significance of this mouse NK cell miRNome.…”

Section: Discussionmentioning

confidence: 99%

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Wang

Zhang

et al. 2012

The Journal of Immunology

121

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NK cells are important innate immune cells with potent cytotoxicity that can be activated by type I IFN from the host once infected. How NK cell cytotoxicity is activated by type I IFN and then tightly regulated remain to be fully elucidated. MicroRNAs (miRNAs, or miRs) are important regulators of innate immune response, but the full scale of miRNome in human NK cells remains to be determined. In this study, we reported an in-depth analysis of miRNomes in resting and IFN-α–activated human NK cells, found two abundant miRNAs, miR-378 and miR-30e, markedly decreased in activated NK cells by IFN-α, and further proved that miR-378 and miR-30e directly targeted granzyme B and perforin, respectively. Thus, IFN-α activation suppresses miR-378 and miR-30e expression to release cytolytic molecule mRNAs for their protein translation and then augments NK cell cytotoxicity. Importantly, the phenomena are also confirmed in human NK cells activated by other cytokines and even in the sorted CD16+CD56dimCD69+ human NK cell subset. Finally, miR-378 and miR-30e were proved to be suppressors of human NK cell cytotoxicity. Taken together, our results reveal that downregulated miR-378 and miR-30e during NK cell activation are negative regulators of human NK cell cytotoxicity, providing a mechanistic explanation for regulation of NK cell function by miRNAs.

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Section: Discussionmentioning

confidence: 99%

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Wang

Zhang

et al. 2012

The Journal of Immunology

121

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“…Sequence variations in mature miRNAs are referred to as isomiRs (11)(12)(13). IsomiRs may be produced by differential excision by DICER1, which can lead to variations in the 5′ and 3′ ends of the mature miRNA (14).…”

Section: Significancementioning

confidence: 99%

PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

Boele

Persson

Shin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

134

138

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Next-generation sequencing experiments have shown that microRNAs (miRNAs) are expressed in many different isoforms (isomiRs), whose biological relevance is often unclear. We found that mature miR-21, the most widely researched miRNA because of its importance in human disease, is produced in two prevalent isomiR forms that differ by 1 nt at their 3′ end, and moreover that the 3′ end of miR-21 is posttranscriptionally adenylated by the noncanonical poly(A) polymerase PAPD5. PAPD5 knockdown caused an increase in the miR-21 expression level, suggesting that PAPD5-mediated adenylation of miR-21 leads to its degradation. Exoribonuclease knockdown experiments followed by small-RNA sequencing suggested that PARN degrades miR-21 in the 3′-to-5′ direction. In accordance with this model, microarray expression profiling demonstrated that PAPD5 knockdown results in a down-regulation of miR-21 target mRNAs. We found that disruption of the miR-21 adenylation and degradation pathway is a general feature in tumors across a wide range of tissues, as evidenced by data from The Cancer Genome Atlas, as well as in the noncancerous proliferative disease psoriasis. We conclude that PAPD5 and PARN mediate degradation of oncogenic miRNA miR-21 through a tailing and trimming process, and that this pathway is disrupted in cancer and other proliferative diseases.nucleotidyl transferase | microRNA processing

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“…In mammals, high-throughput sequencing methods that have contributed to miRNA discovery efforts have included massively parallel signature sequencing (MPSS) (Mineno et al 2006), miRNA serial analysis of gene expression (miRAGE) (Cummins et al 2006), 454 pyrosequencing (Berezikov et al 2006a(Berezikov et al , 2007Calabrese et al 2007), and Illumina sequencing (Babiarz et al 2008;Kuchenbauer et al 2008). …”

mentioning

confidence: 99%

Mammalian microRNAs: experimental evaluation of novel and previously annotated genes

Chiang

Schoenfeld²,

Ruby³

et al. 2010

Genes Dev.

732

756

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MicroRNAs (miRNAs) are small regulatory RNAs that derive from distinctive hairpin transcripts. To learn more about the miRNAs of mammals, we sequenced 60 million small RNAs from mouse brain, ovary, testes, embryonic stem cells, three embryonic stages, and whole newborns. Analysis of these sequences confirmed 398 annotated miRNA genes and identified 108 novel miRNA genes. More than 150 previously annotated miRNAs and hundreds of candidates failed to yield sequenced RNAs with miRNA-like features. Ectopically expressing these previously proposed miRNA hairpins also did not yield small RNAs, whereas ectopically expressing the confirmed and newly identified hairpins usually did yield small RNAs with the classical miRNA features, including dependence on the Drosha endonuclease for processing. These experiments, which suggest that previous estimates of conserved mammalian miRNAs were inflated, provide a substantially revised list of confidently identified murine miRNAs from which to infer the general features of mammalian miRNAs. Our analyses also revealed new aspects of miRNA biogenesis and modification, including tissue-specific strand preferences, sequential Dicer cleavage of a metazoan precursor miRNA (pre-miRNA), consequential 59 heterogeneity, newly identified instances of miRNA editing, and evidence for widespread pre-miRNA uridylation reminiscent of miRNA regulation by Lin28.[Keywords: MicroRNA; miRNA biogenesis; noncoding RNA genes; high-throughput sequencing] Supplemental material is available at http://www.genesdev.org.

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In-depth characterization of the microRNA transcriptome in a leukemia progression model

Cited by 164 publications

References 64 publications

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity

PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

Mammalian microRNAs: experimental evaluation of novel and previously annotated genes

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