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Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation

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 resulta...

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Autores principales: Tan, Shen Mynn, Altschuler, Gabriel, Zhao, Tian Yun, Ang, Haw Siang, Yang, Henry, Lim, Bing, Vardy, Leah, Hide, Winston, Thomson, Andrew M., Lareu, Ricky R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081066/
https://www.ncbi.nlm.nih.gov/pubmed/24860167
http://dx.doi.org/10.1093/nar/gku430
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author Tan, Shen Mynn
Altschuler, Gabriel
Zhao, Tian Yun
Ang, Haw Siang
Yang, Henry
Lim, Bing
Vardy, Leah
Hide, Winston
Thomson, Andrew M.
Lareu, Ricky R.
author_facet Tan, Shen Mynn
Altschuler, Gabriel
Zhao, Tian Yun
Ang, Haw Siang
Yang, Henry
Lim, Bing
Vardy, Leah
Hide, Winston
Thomson, Andrew M.
Lareu, Ricky R.
author_sort Tan, Shen Mynn
collection PubMed
description 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.
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spelling pubmed-40810662014-07-10 Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation Tan, Shen Mynn Altschuler, Gabriel Zhao, Tian Yun Ang, Haw Siang Yang, Henry Lim, Bing Vardy, Leah Hide, Winston Thomson, Andrew M. Lareu, Ricky R. Nucleic Acids Res RNA 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. Oxford University Press 2014-08-01 2014-05-23 /pmc/articles/PMC4081066/ /pubmed/24860167 http://dx.doi.org/10.1093/nar/gku430 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Tan, Shen Mynn
Altschuler, Gabriel
Zhao, Tian Yun
Ang, Haw Siang
Yang, Henry
Lim, Bing
Vardy, Leah
Hide, Winston
Thomson, Andrew M.
Lareu, Ricky R.
Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation
title Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation
title_full Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation
title_fullStr Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation
title_full_unstemmed Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation
title_short Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation
title_sort divergent lin28-mrna associations result in translational suppression upon the initiation of differentiation
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081066/
https://www.ncbi.nlm.nih.gov/pubmed/24860167
http://dx.doi.org/10.1093/nar/gku430
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