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miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively

miRNAs typically downregulate the expression of target genes by binding to their 3′UTR, and dysregulation of miRNAs may contribute to tumorigenesis. Here, we found that miR-346 and miR-138 competitively bind to a common region in the 3′UTR of hTERT mRNA and have opposite effects on the expression an...

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Autores principales: Song, Ge, Wang, Renjie, Guo, Junfei, Liu, Xuyuan, Wang, Fang, Qi, Ying, Wan, Haiying, Liu, Min, Li, Xin, Tang, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623477/
https://www.ncbi.nlm.nih.gov/pubmed/26507454
http://dx.doi.org/10.1038/srep15793
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author Song, Ge
Wang, Renjie
Guo, Junfei
Liu, Xuyuan
Wang, Fang
Qi, Ying
Wan, Haiying
Liu, Min
Li, Xin
Tang, Hua
author_facet Song, Ge
Wang, Renjie
Guo, Junfei
Liu, Xuyuan
Wang, Fang
Qi, Ying
Wan, Haiying
Liu, Min
Li, Xin
Tang, Hua
author_sort Song, Ge
collection PubMed
description miRNAs typically downregulate the expression of target genes by binding to their 3′UTR, and dysregulation of miRNAs may contribute to tumorigenesis. Here, we found that miR-346 and miR-138 competitively bind to a common region in the 3′UTR of hTERT mRNA and have opposite effects on the expression and function of hTERT in human cervical cancer cells. Furthermore, G-rich RNA sequence binding factor 1 (GRSF1) mediates the miR-346-dependent upregulation of hTERT by binding to the miR-346 middle sequence motif (CCGCAU) which forms a “bulge loop” when miR-346 is bound to the hTERT 3′UTR, facilitating the recruitment of hTERT mRNA to ribosomes to promote translation in an AGO2-independent manner. Conversely, miR-138 suppresses hTERT expression in an AGO2-dependent manner. Interestingly, replacement of the miR-138 middle sequence with that of miR-346 results in an upregulation of hTERT expression in a GRSF1-dependent manner. Moreover, miR-346 depends on GRSF1 to upregulate another target gene, activin A receptor, type IIB (ACVR2B), in which miR-346 “CCGCAU” motif is essential. These findings reveal novel mechanisms of miRNA-mediated upregulation of target gene expression and describe the coordinated action of multiple miRNAs to control the fate of a single target mRNA through binding to its 3′UTR.
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spelling pubmed-46234772015-11-03 miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively Song, Ge Wang, Renjie Guo, Junfei Liu, Xuyuan Wang, Fang Qi, Ying Wan, Haiying Liu, Min Li, Xin Tang, Hua Sci Rep Article miRNAs typically downregulate the expression of target genes by binding to their 3′UTR, and dysregulation of miRNAs may contribute to tumorigenesis. Here, we found that miR-346 and miR-138 competitively bind to a common region in the 3′UTR of hTERT mRNA and have opposite effects on the expression and function of hTERT in human cervical cancer cells. Furthermore, G-rich RNA sequence binding factor 1 (GRSF1) mediates the miR-346-dependent upregulation of hTERT by binding to the miR-346 middle sequence motif (CCGCAU) which forms a “bulge loop” when miR-346 is bound to the hTERT 3′UTR, facilitating the recruitment of hTERT mRNA to ribosomes to promote translation in an AGO2-independent manner. Conversely, miR-138 suppresses hTERT expression in an AGO2-dependent manner. Interestingly, replacement of the miR-138 middle sequence with that of miR-346 results in an upregulation of hTERT expression in a GRSF1-dependent manner. Moreover, miR-346 depends on GRSF1 to upregulate another target gene, activin A receptor, type IIB (ACVR2B), in which miR-346 “CCGCAU” motif is essential. These findings reveal novel mechanisms of miRNA-mediated upregulation of target gene expression and describe the coordinated action of multiple miRNAs to control the fate of a single target mRNA through binding to its 3′UTR. Nature Publishing Group 2015-10-28 /pmc/articles/PMC4623477/ /pubmed/26507454 http://dx.doi.org/10.1038/srep15793 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Song, Ge
Wang, Renjie
Guo, Junfei
Liu, Xuyuan
Wang, Fang
Qi, Ying
Wan, Haiying
Liu, Min
Li, Xin
Tang, Hua
miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively
title miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively
title_full miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively
title_fullStr miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively
title_full_unstemmed miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively
title_short miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively
title_sort mir-346 and mir-138 competitively regulate htert in grsf1- and ago2-dependent manners, respectively
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623477/
https://www.ncbi.nlm.nih.gov/pubmed/26507454
http://dx.doi.org/10.1038/srep15793
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