MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation

Abstract

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.

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

“…It is generally believed that the mature miRNA then incorporates into the RNA-induced silencing complex, and guides this complex to the 3'-untranslated region (3'-UTR) of specific target mRNA transcripts to suppress translation or induce their degradation [1,2,[10][11][12][13] . However, miRNAbinding sites in coding regions as well as in the 5'-UTRs have also been reported [14][15][16][17][18][19] .…”

DeepScreen: An Accurate, Rapid, and Anti‐Interference Screening Approach for Nanoformulated Medication by Deep Learning

“…Since DeepScreen has the ability to extract the features by itself, possible upgrades for application could be expected to detect other cellular state changes such as stem cell differentiation. Related markers like Oct4, Sox2, etc., could be stained and detection by Flowsight,48 and the collected labeled images could be analyzed by our approach, a prediction system for stem cell differentiation could be built by training.…”

Isolation and characterization of mesenchymal progenitors derived from the bone marrow of goats native from northeastern Brazil

“…Pan and Thonsom 45 showed that only the LIF/ OCT-4 pathway is insufficient to prevent cell differentiation events, suggesting that other factors could also be committed in the preservation of this feature. Mitsui et al 46 found high concentrations of mRNA Nanog within the morula stage during embryonic development, and likewise, Tay et al 47 found that in the absence of OCT-3/4 and LIF, Nanog is capable of maintaining a pluripotent cell. Riekstina et al 48 al.…”