The big world of small RNAs

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Science (Impact Factor: 33.61). 10/2005; 309(5740):1519-24. DOI: 10.1126/science.1111444
Source: PubMed


Small RNA guides—microRNAs, small interfering RNAs, and repeat-associated small interfering RNAs, 21 to 30 nucleotides in
length—shape diverse cellular pathways, from chromosome architecture to stem cell maintenance. Fifteen years after the discovery
of RNA silencing, we are only just beginning to understand the depth and complexity of how these RNAs regulate gene expression
and to consider their role in shaping the evolutionary history of higher eukaryotes.

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    • "MicroRNAs (miRs) are small (20–22 nt long) noncoding RNAs that suppress protein translation by binding to target mRNAs, reducing their stability and/or inhibiting translation. These molecules are crucially important in specifying cell differentiation [9] [10], therefore contributing to developmental patterning and regeneration processes. Several miRs, including miRs of 17–92a cluster, miR-24 and miR-200b, which collectively referred to as angio-miRs are involved in pathways modulating angiogenesis [11] [12]. "
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    ABSTRACT: Mesenchymal stromal cells including those from adipose tissue (MSCs) regulate angiogenesis in adult tissues. MicroRNAs (miRs), small noncoding RNAs that control gene expression by binding to target mRNAs, reducing their stability and/or inhibiting translation, appear to be important regulators of blood vessel growth. In this study, we examined the impact of angio-miRs on paracrine activities of MSCs. Using Illumina microarrays we found that miR-92a is the one of the most abundant angio-miRs in human MSCs. We transfected MSC with pre-miR-92a or anti-miR-92a which led to the coordinated changes of known miR-92a target mRNA levels. Then we tested the ability of conditioned medium from transfected cells to stimulate tube formation by HUVECs. MSC overexpressing miR-92a completely lost the ability to stimulate tubes formation by endothelial cells. However, knocking-out miR-92a by transfection with anti-miR-92a did not increase the ability of MSC to stimulate tube formation. Secretion of hepatocyte growth factor (HGF) and angiopoetin-1 was significantly lower in the medium of miR-92a overexpressing MSC, whereas VEGF secretion did not change significantly. The replenishment of HGF but not angiopoietin-1 has restored the ability of conditioned medium from miR-92a overexpressing MSC to stimulate the tube formation. We conclude that overexpression of miR-92a in MSC suppresses angiogenic properties of these cells by down-regulation of HGF secretion.
    Experimental Cell Research 10/2015; DOI:10.1016/j.yexcr.2015.10.007 · 3.25 Impact Factor
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    • "MiRNAs are a class of noncoding RNA duplex molecules that are approximately 21–23 nucleotides in length, which regulate the stability or the translational efficiency of target mRNAs (Zamore and Haley, 2005). MiRNAs are formed through primary transcription in the nucleus by means of RNA polymerase , also referred to as long primary transcripts (pre-miRNAs), processed into 70-to 100-nucleotide sequences by RNAse III Drosha, and then exported into the cytoplasm where they are further processed to generate mature miRNA species of the form of double stranded RNAs (Vasudevan et al., 2007). "
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    • "Let-7a was found to regulate the drug-induced apoptosis in cells by targeting caspase-3 [127]. Many studies reported that let-7a may serve as tumor suppressor miRNAs because of its downregulation in association with the overexpression of oncogenes as RAS and HMGA2 [127] [128]. Besides, let-7 also modulates cell proliferation [129]. "
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    ABSTRACT: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. MicroRNAs (miRNAs) are naturally-occurring, non-coding small RNA molecules that can modulate protein coding-genes, which makes it contributing to nearly all the physiological and pathological processes. Progression of breast cancer and resistance to endocrine therapies has been attributed to the possibility of hormone-responsive miRNAs involved in the regulation of certain signaling pathways. Methodology This review introduces better understanding of miRNAs to provide promising advances for treatment. miRNAs have multiple targets, and they were found to regulate different signaling pathways; consequently it is important to characterize their mechanisms of action and their cellular targets in order to introduce miRNAs as novel and promising therapies. This review summarizes the molecular mechanisms of miRNAs in TGF-Beta signaling, apoptosis, metastasis, cell cycle, ER-signaling, and drug resistance. Finally, miRNAs will be introduced as promising molecules to be used in the fight against breast cancer and its developed drug resistance. Copyright © 2014. Published by Elsevier Inc.
    Clinical Biochemistry 12/2014; 48(6). DOI:10.1016/j.clinbiochem.2014.12.013 · 2.28 Impact Factor
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