Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation
| Autor: | Ricky R. Lareu, Haw Siang Ang, Andrew M. Thomson, Henry Yang, Shen Mynn Tan, Winston Hide, Bing Lim, Tian Yun Zhao, Leah A. Vardy, Gabriel Altschuler |
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| Rok vydání: | 2014 |
| Předmět: |
Translational efficiency
Cellular differentiation Wnt signaling pathway RNA-Binding Proteins Cell Differentiation Biology LIN28 Embryonic stem cell Cell biology Polyribosomes Protein Biosynthesis Translational regulation microRNA Genetics RNA Humans RNA Messenger Induced pluripotent stem cell Cells Cultured Embryonic Stem Cells |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gku430 |
| Popis: | LIN28 function is fundamental to the activity and behavior of human embryonic stem cells (hESCs) and induced pluripotent stem cells. Its main roles in these cell types are the regulation of translational efficiency and let-7 miRNA maturation. However, LIN28-associated mRNA cargo shifting and resultant regulation of translational efficiency upon the initiation of differentiation remain unknown. An RNA-immunoprecipitation and microarray analysis protocol, eRIP, that has high specificity and sensitivity was developed to test endogenous LIN28-associated mRNA cargo shifting. A combined eRIP and polysome analysis of early stage differentiation of hESCs with two distinct differentiation cues revealed close similarities between the dynamics of LIN28 association and translational modulation of genes involved in the Wnt signaling, cell cycle, RNA metabolism and proteasomal pathways. Our data demonstrate that change in translational efficiency is a major contributor to early stages of differentiation of hESCs, in which LIN28 plays a central role. This implies that eRIP analysis of LIN28-associated RNA cargoes may be used for rapid functional quality control of pluripotent stem cells under manufacture for therapeutic applications. |
| Databáze: | OpenAIRE |
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