From microRNAs to targets: Pathway discovery in cell fate transitions

Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Department of Urology, University of California San Francisco, San Francisco, CA, USA.
Current opinion in genetics & development (Impact Factor: 7.57). 05/2011; 21(4):498-503. DOI: 10.1016/j.gde.2011.04.011
Source: PubMed


MicroRNAs (miRNAs) are 22 nt non-coding RNAs that regulate expression of downstream targets by messenger RNA (mRNA) destabilization and translational inhibition. A large number of eukaryotic mRNAs are targeted by miRNAs, with many individual mRNAs being targeted by multiple miRNAs. Further, a single miRNA can target hundreds of mRNAs, making these small RNAs powerful regulators of cell fate decisions. Such regulation by miRNAs has been observed in the maintenance of the embryonic stem cell (ESC) cell cycle and during ESC differentiation. MiRNAs can also promote the dedifferentiation of somatic cells to induced pluripotent stem cells. During this process they target multiple downstream genes, which represent important nodes of key cellular processes. Here, we review these findings and discuss how miRNAs may be used as tools to discover novel pathways that are involved in cell fate transitions using dedifferentiation of somatic cells to induced pluripotent stem cells as a case study.

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Available from: Robert Blelloch, Apr 23, 2015
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    • "Following export from the nucleus into the cytoplasm by exportin-5 [16], [17], the pre-miRNAs are processed by Dicer into a single-stranded mature miRNA of ∼22 nucleotides in length, which is then incorporated into the miRNA-induced silencing complex (miRISC) [18], [19]. The mature miRNA in the RISC complex can bind to target mRNAs with full or partial base complementarity and can downregulate gene expression by translational repression or mRNA cleavage [20]. "
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    • "MicroRNAs were discovered as small temporal RNAs that regulate developmental transitions in C. elegans. They have diverse expressive patterns and regulate a variety of areas, including embryologic development, physiology, pathophysiology, and growth, development, progression, and metastasis in cancer [15–17]. Currently, there are 2,578 (human) and 1908 (mouse) mature unique miRNAs identified (mirBase 20, June 2013), and more than half are conserved in vertebrates [18]. "
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    • "Abbreviations used AGO, Argonaute sub-family of Argonaute proteins; Armi, Armitage; Aub, Aubergine; HP1, heterochromatin protein 1; LINE, long interspersed nuclear element; LTR, long terminal repeat elements; miRNAs, microRNAs; piRNAs, PIWI-interacting RNAs; PIWI, Piwi sub-family of Argonaute proteins; SINE, short interspersed nuclear element; siRNAs, smallinterfering RNAs; UTR, untranslated region; Vret, Vreteno; Zuc, Zucchini yeast and plants, thereby silencing gene transcription (Martienssen et al., 2008). The profound impact of small RNA pathways on gene regulation is obvious from the significant roles they play in a variety of biological processes including stem cell self-renewal and differentiation (Gangaraju and Lin, 2009; Subramanyam and Blelloch, 2011), various aspects of animal development (Stefani and Slack, 2008), germline development (Saxe and Lin, 2011), and human diseases including cancer (Esteller, 2011). It is increasingly clear that small RNA pathways exert significant control over the expression of large numbers of genes, and therefore can exert significant influence over gene networks. "
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