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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: 8.57). 05/2011; 21(4):498-503. DOI: 10.1016/j.gde.2011.04.011
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ABSTRACT 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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    • "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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    Molecular Reproduction and Development 08/2013; 80(8). DOI:10.1002/mrd.22195 · 2.68 Impact Factor
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    • "(legend continued on next page) iPSC-inhibitory factor Prrx1 (Yang et al., 2011) is predicted to be targeted by miR-294. Unexpectedly, miR-302a, whose forced expression was also shown to enhance iPSC generation in the context of the Yamanaka factors (Subramanyam and Blelloch, 2011), exhibited transient activation specifically in Oct4-GFP+ cells at day 12 but remained otherwise unchanged (Figures S3G and S3H). Mir-302a is normally expressed in mouse epiblast stem cells (Huo and Zambidis, 2012) but barely detectable in mouse ESCs, suggesting that iPSC induction might entail a transient passage through an epiblast-like state before reaching naive pluripotency. "
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    Cell 12/2012; 151(7):1617-32. DOI:10.1016/j.cell.2012.11.039 · 33.12 Impact Factor
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