Biochemical mechanisms of the RNA-induced silencing complex

Paroo, Zain; Liu, Qinghua; Wang, Xiaodong

doi:10.1038/sj.cr.7310148

Cited by 38 publications

(38 citation statements)

References 73 publications

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“…The primary miRNA transcript, namely pri-miRNAs, is several kilobases long and undergoes substantial processing in the nucleus, resulting in the generation of a 70-to 90-nt stem-loop precursor miRNA (pre-miRNA). After subsequent processing in the cytoplasm by Dicer, a double-stranded miRNA duplex, which contains 2 nt-long 3 0 overhangs that will unwind and form a single-stranded mature miRNA, is generated (Bernstein et al 2001, Bernstein et al 2003, Paroo et al 2007. The mature miRNAs repress translation or assist in mRNA degradation in a sequence-specific manner (Ambros 2004, Bartel 2004, Zamore & Haley 2005.…”

Section: Introductionmentioning

confidence: 99%

Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis

Yang

Zhou²,

Peng³

et al. 2012

Reproduction

157

122

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Recent studies implicate the regulatory function of microRNAs (miRNAs) in oocyte maturation and ovarian follicular development. Differentially expressed miRNAs are found in the plasma of premature ovarian failure (POF) patients and normal cycling women. In this study, miRNA-regulated signaling pathways and related genes were described using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The effect of mir-23a on granulosa cell apoptosis was also studied by examining the protein expression of X-linked inhibitor of apoptosis protein (XIAP) and caspase-3, followed by subsequent counting of apoptotic cells after Hoechst 33258 staining. Both GO analysis and pathway analysis suggested that many signaling pathways, including the AKT signaling pathway, steroid hormone receptor signaling pathways, and others, were regulated by this group of differentially expressed miRNAs. A decrease in XIAP expression (mRNA and protein level) and caspase-3 protein levels and an increase in cleaved caspase-3 protein were observed in human ovarian granulosa cells transfected with pre-mir-23a, along with an increased occurrence of apoptosis. In conclusion, differentially expressed miRNAs in the plasma of POF patients may have regulatory effects on proliferation and apoptosis of granulosa cells by affecting different signaling pathways. Mir-23a may play important roles in regulating apoptosis via decreasing XIAP expression in human ovarian granulosa cells.

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Section: Introductionmentioning

confidence: 99%

Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis

Yang

Zhou²,

Peng³

et al. 2012

Reproduction

157

122

View full text Add to dashboard Cite

show abstract

“…RNA interference (RNAi) is a post-transcriptional gene silencing mechanism guided by 21-to 25-nucleotide(nt) small interfering RNAs (siRNAs) and microRNAs (miRNAs) (Fire et al 1998;Hannon 2002;Tomari and Zamore 2005;Paroo et al 2007). The catalytic engine of RNAi consists of two enzymes, Dicer and Argonaute (Ago) (Paroo et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Dicer-1, but not Loquacious, is critical for assembly of miRNA-induced silencing complexes

Liu

Park

Jiang

et al. 2007

RNA

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Double-stranded RNA-binding proteins (dsRBPs), such as R2D2 and Loquacious (Loqs), function in tandem with Dicer (Dcr) enzymes in RNA interference (RNAi). In Drosophila, Dcr-1/Loqs and Dcr-2/R2D2 complexes generate microRNAs (miRNAs) and small interfering RNAs (siRNAs), respectively. Although R2D2 does not regulate siRNA production, R2D2 and Dcr-2 coordinately bind siRNAs to promote assembly of the siRNA-induced silencing (siRISC) complexes. Conversely, Loqs enhances miRNA production. It is uncertain if Dcr-1 and Loqs facilitate miRNA loading onto the miRISC complexes. Here we used loqs knockout (KO) flies to characterize the physiological functions of Loqs in the miRNA pathway. Northern analysis revealed consistent accumulation of precursor (pre)-miRNAs in loqs KO flies. However, the lack of Loqs had differential effects on mature miRNAs: some are diminished, whereas others maintain wild-type levels. Importantly, the data suggest that miRNA production is not the rate-limiting step of the miRNA pathway. We show that Dcr-1, but not Loqs, is critical for assembly of miRISCs by using dcr-1 or loqs null egg extract. Consistent with this, recombinant Dcr-1 could efficiently interact with miRNA duplex in the absence of Loqs. Together, our results indicate that Loqs plays a prominent role in miRNA biogenesis, but is largely dispensable for miRISC assembly. Thus, Loqs and R2D2 represent two distinct functional modes for dsRBPs in the RNAi pathways.

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“…Typically, Dicer functions in tandem with a specific dsRNAbinding protein (5). For example, Dcr-2 and R2D2 constitute the Drosophila, siRNA-generating enzyme (24).…”

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confidence: 99%

Functional Anatomy of the Drosophila MicroRNA-generating Enzyme

Paroo

Liu

2007

Journal of Biological Chemistry

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In Drosophila melanogaster, the multidomain RNase III Dicer-1 (Dcr-1) functions in tandem with the doublestranded (ds)RNA-binding protein Loquacious (Loqs) to catalyze the maturation of microRNAs (miRNAs) from precursor (pre)-miRNAs. Here we dissect the molecular mechanism of pre-miRNA processing by the Dcr-1-Loqs complex. The tandem RNase III (RIII) domains of Dcr-1 form an intramolecular dimer such that one RIII domain cleaves the 3 strand, whereas the other cuts the 5 strand of pre-miRNA. We show that the functional core of Dcr-1 consists of a DUF283 domain, a PAZ domain, and two RIII domains. Dcr-1 preferentially associates with the Loqs-PB splice isoform. Loqs-PB uses the second dsRNA-binding domain to bind pre-miRNA and the third dsRNA-binding domain to interact with Dcr-1. Both domains of Loqs-PB are required for efficient miRNA production by enhancing the affinity of Dcr-1 for pre-miRNA. Thus, our results provide further insights into the functional anatomy of the Drosophila miRNA-generating enzyme.

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Biochemical mechanisms of the RNA-induced silencing complex

Cited by 38 publications

References 73 publications

Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis

Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis

Dicer-1, but not Loquacious, is critical for assembly of miRNA-induced silencing complexes

Functional Anatomy of the Drosophila MicroRNA-generating Enzyme

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