The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy

Ross, Jason P.; Kassir, Zena

doi:10.1038/mtna.2014.54

Cited by 15 publications

(14 citation statements)

References 121 publications

(225 reference statements)

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“…In addition to miRNA mediated post-transcriptional gene silencing, AGO proteins are reported to perform various moonlighting functions in other subcellular compartments. Nuclear localized AGO proteins regulate transcriptional silencing, epigenetic modulation, alternative splicing, and DNA repair (Huang and Li, 2014;Ross and Kassir, 2014). The function of nuclear-localized AGO complexes has been previously reviewed and hence will not be discussed further in this review (Huang and Li, 2014;Ross and Kassir, 2014;Kalantari et al, 2016;Sharma et al, 2016;Liu et al, 2018).…”

Section: Diverse Mirisc Composition and Its Regulation Brings About Tmentioning

confidence: 99%

The Role of Dynamic miRISC During Neuronal Development

Nawalpuri

Ravindran

Muddashetty

2020

Front. Mol. Biosci.

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Activity-dependent protein synthesis plays an important role during neuronal development by fine-tuning the formation and function of neuronal circuits. Recent studies have shown that miRNAs are integral to this regulation because of their ability to control protein synthesis in a rapid, specific and potentially reversible manner. miRNA mediated regulation is a multistep process that involves inhibition of translation before degradation of targeted mRNA, which provides the possibility to store and reverse the inhibition at multiple stages. This flexibility is primarily thought to be derived from the composition of miRNA induced silencing complex (miRISC). AGO2 is likely the only obligatory component of miRISC, while multiple RBPs are shown to be associated with this core miRISC to form diverse miRISC complexes. The formation of these heterogeneous miRISC complexes is intricately regulated by various extracellular signals and cell-specific contexts. In this review, we discuss the composition of miRISC and its functions during neuronal development. Neurodevelopment is guided by both internal programs and external cues. Neuronal activity and external signals play an important role in the formation and refining of the neuronal network. miRISC composition and diversity have a critical role at distinct stages of neurodevelopment. Even though there is a good amount of literature available on the role of miRNAs mediated regulation of neuronal development, surprisingly the role of miRISC composition and its functional dynamics in neuronal development is not much discussed. In this article, we review the available literature on the heterogeneity of the neuronal miRISC composition and how this may influence translation regulation in the context of neuronal development.

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Section: Diverse Mirisc Composition and Its Regulation Brings About Tmentioning

confidence: 99%

The Role of Dynamic miRISC During Neuronal Development

Nawalpuri

Ravindran

Muddashetty

2020

Front. Mol. Biosci.

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“…An example is the finding that Drosha, and not Dicer, regulated the proliferation of hMSCs through a miRNA independent mechanism, potentially by regulating ribosomal RNA processing [50]. Also, Argo proteins are mainly in the cytoplasm (canonical pathway) but are also found in the nucleus where they may have transcriptional functions independent of miRNA processing [51]. …”

Section: Biogenesis and Regulation Of Mirnas: Complexity For Divermentioning

confidence: 99%

Non-coding RNAs: Epigenetic regulators of bone development and homeostasis

Hassan

Tye

Stein

et al. 2015

Bone

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Non-coding RNAs (ncRNAs) have evolved in eukaryotes as epigenetic regulators of gene expression. The most abundant regulatory ncRNAs are the 20–24 nt small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs, <200 nt). Each class of ncRNAs operates through distinct mechanisms, but their pathways to regulating gene expression are interrelated in ways that are just being recognized. While the importance of lncRNAs in epigenetic control of transcription, developmental processes and human traits is emerging, the identity of lncRNAs in skeletal biology is scarcely known. However, since the first profiling studies of miRNA at stages during osteoblast and osteoclast differentiation, over 1100 publications related to bone biology and pathologies can be found, as well as many recent comprehensive reviews summarizing miRNA in skeletal cells. Delineating the activities and targets of specific miRNAs regulating differentiation of osteogenic and resorptive bone cells, coupled with in vivo gain-and loss-of-function studies, discovered unique mechanisms that support bone development and bone homeostasis in adults. We present here “guiding principles” for addressing biological control of bone tissue formation by ncRNAs. This review emphasizes recent advances in understanding regulation of the process of miRNA biogenesis that impact on osteogenic lineage commitment, transcription factors and signaling pathways. Also discussed are the approaches to be pursued for an understanding of the role of lncRNAs in bone and the challenges in addressing their multiple and complex functions. Based on new knowledge of epigenetic control of gene expression to be gained for ncRNA regulation of the skeleton, new directions for translating the miRNAs and lncRNAs into therapeutic targets for skeletal disorders are possible.

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“…In the cytoplasm, Ago proteins are critical for processing of miRNAs and for post-transcriptional gene silencing in complex with RNA induced silencing complex, RISC. In addition, an emerging function of nuclear Ago proteins involves the epigenetic control of gene expression via the recruitment of chromatin modifiers (e.g., H3K9 and H3K4 methytransferases), resulting in either repression or activation of gene expression ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Epigenome Engineering in Cancer: Fairytale or a Realistic Path to the Clinic?

2015

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Epigenetic modifications such as histone post-transcriptional modifications, DNA methylation, and non-protein-coding RNAs organize the DNA in the nucleus of eukaryotic cells and are critical for the spatio-temporal regulation of gene expression. These epigenetic modifications are reversible and precisely regulated by epigenetic enzymes. In addition to genetic mutations, epigenetic modifications are highly disrupted in cancer relative to normal tissues. Many epigenetic alterations (epi-mutations) are associated with aberrations in the expression and/or activity of epigenetic enzymes. Thus, epigenetic regulators have emerged as prime targets for cancer therapy. Currently, several inhibitors of epigenetic enzymes (epi-drugs) have been approved for use in the clinic to treat cancer patients with hematological malignancies. However, one potential disadvantage of epi-drugs is their lack of locus-selective specificity, which may result in the over-expression of undesirable parts of the genome. The emerging and rapidly growing field of epigenome engineering has opened new grounds for improving epigenetic therapy in view of reducing the genome-wide “off-target” effects of the treatment. In the current review, we will first describe the language of epigenetic modifications and their involvement in cancer. Next, we will overview the current strategies for engineering of artificial DNA-binding domains in order to manipulate and ultimately normalize the aberrant landscape of the cancer epigenome (epigenome engineering). Lastly, the potential clinical applications of these emerging genome-engineering approaches will be discussed.

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The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy

Cited by 15 publications

References 121 publications

The Role of Dynamic miRISC During Neuronal Development

The Role of Dynamic miRISC During Neuronal Development

Non-coding RNAs: Epigenetic regulators of bone development and homeostasis

Epigenome Engineering in Cancer: Fairytale or a Realistic Path to the Clinic?

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