MicroRNAs (miRNAs) are short RNAs that direct messenger RNA degradation or disrupt mRNA translation in a sequence-dependent manner. For more than a decade, attempts to study the interaction of miRNAs with their targets were confined to the 3' untranslated regions of mRNAs, fuelling an underlying assumption that these regions are the principal recipients of miRNA activity. Here we focus on the mouse Nanog, Oct4 (also known as Pou5f1) and Sox2 genes and demonstrate the existence of many naturally occurring miRNA targets in their amino acid coding sequence (CDS). Some of the mouse targets analysed do not contain the miRNA seed, whereas others span exon-exon junctions or are not conserved in the human and rhesus genomes. miR-134, miR-296 and miR-470, upregulated on retinoic-acid-induced differentiation of mouse embryonic stem cells, target the CDS of each transcription factor in various combinations, leading to transcriptional and morphological changes characteristic of differentiating mouse embryonic stem cells, and resulting in a new phenotype. Silent mutations at the predicted targets abolish miRNA activity, prevent the downregulation of the corresponding genes and delay the induced phenotype. Our findings demonstrate the abundance of CDS-located miRNA targets, some of which can be species-specific, and support an augmented model whereby animal miRNAs exercise their control on mRNAs through targets that can reside beyond the 3' untranslated region.
"One of the important factors involved in self-renewal and maintenance of HSCs multipotency of CD34 stem cells is Sall4 transcription factor (TF) (Aguila et al., 2011). Sall4 is zinc-finger TF belong to spalt-1ike protein family, located on chromosome 20 and expressed in undifferentiated stem cells like normally embryonic stem cells (ESCs) and CD34 + HSCs (Tay et al., 2008). Sall4 binds to regulatory regions of ESCs master regulators such as Nanog and Oct-4 and regulates their expression (Wu et al., 2006; Zhang et al., 2006; Tan et al., 2013). "
"MicroRNAs are a class of 17–24 nt small, noncoding RNAs, which mediate post-transcriptional gene silencing by binding to the 3-untranslated region (UTR) or open reading frame (ORF) region of target mRNAs . The involvement of miRNAs in many biological activities has been well documented, including cell proliferation, cell differentiation, cell migration, disease initiation, and disease progression     . "
"This phenomenon may be somewhat exaggerated, however, as many miRNA target prediction programs consider only 3 0 -UTRs in predictions of miRNA binding (Lewis et al. 2005; Wang and El Naqa 2008; Maragkakis et al. 2009). Indeed, miRNA target sites located within coding sequences have been documented in animals (Forman et al. 2008; Tay et al. 2008), including humans (Forman et al. 2008), and have recently been suggested to be a common occurrence in cnidarians (Moran et al. 2014). There is some evidence suggesting that miRNA binding in coding regions may require higher sequence complementarity between the miRNA and its target, and proceed via RISC-mediated cleavage (Duursma et al. 2008). "
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