HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6

Summary: The functional inactivation of tumor suppressor microRNA (miRNA) is closely related to the tumorigenesis of cancer. There are instances where the miRNA and the corresponding target both exist in a cell, but the target gene silencing do not occur as expected. Herein, we found that both miR-5...

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Autores principales: Menghui Yin, Meidie Cheng, Chengli Liu, Keli Wu, Wei Xiong, Ji Fang, Yinxiong Li, Biliang Zhang
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Publicado: Elsevier 2021
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spelling oai:doaj.org-article:8faa0f143d804ab5b62bfd656793089d2021-11-20T05:10:15ZHNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK62589-004210.1016/j.isci.2021.103345https://doaj.org/article/8faa0f143d804ab5b62bfd656793089d2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013146https://doaj.org/toc/2589-0042Summary: The functional inactivation of tumor suppressor microRNA (miRNA) is closely related to the tumorigenesis of cancer. There are instances where the miRNA and the corresponding target both exist in a cell, but the target gene silencing do not occur as expected. Herein, we found that both miR-506 and its target CDK6 are highly co-expressed in lung cancer cells. Sequence analyses suggested that a miR-506 binding site (1648–1654) and a cis-element (1785–1795) for binding by heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) are evolutionarily conserved and forms a stem structure in the 3′ untranslated region (3′UTR) of CDK6. Furthermore, HNRNPA2B1 can bind to the stem structure to denature it and recruit the RNA helicase DExH-box helicase 9 (DHX9) to the 3′UTR, which ultimately facilitates miRNAs-mediated CDK6 silencing. These results indicate that the cis-element of the 3′UTR of CDK6, where HNRNPA2B1 binds, serves as an RNA switch to regulate miRNAs’ function in cancer cells.Menghui YinMeidie ChengChengli LiuKeli WuWei XiongJi FangYinxiong LiBiliang ZhangElsevierarticleBiological sciencesBiochemistryMolecular biologyCell biologyScienceQENiScience, Vol 24, Iss 11, Pp 103345- (2021)
institution DOAJ
collection DOAJ
language EN
topic Biological sciences
Biochemistry
Molecular biology
Cell biology
Science
Q
spellingShingle Biological sciences
Biochemistry
Molecular biology
Cell biology
Science
Q
Menghui Yin
Meidie Cheng
Chengli Liu
Keli Wu
Wei Xiong
Ji Fang
Yinxiong Li
Biliang Zhang
HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6
description Summary: The functional inactivation of tumor suppressor microRNA (miRNA) is closely related to the tumorigenesis of cancer. There are instances where the miRNA and the corresponding target both exist in a cell, but the target gene silencing do not occur as expected. Herein, we found that both miR-506 and its target CDK6 are highly co-expressed in lung cancer cells. Sequence analyses suggested that a miR-506 binding site (1648–1654) and a cis-element (1785–1795) for binding by heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) are evolutionarily conserved and forms a stem structure in the 3′ untranslated region (3′UTR) of CDK6. Furthermore, HNRNPA2B1 can bind to the stem structure to denature it and recruit the RNA helicase DExH-box helicase 9 (DHX9) to the 3′UTR, which ultimately facilitates miRNAs-mediated CDK6 silencing. These results indicate that the cis-element of the 3′UTR of CDK6, where HNRNPA2B1 binds, serves as an RNA switch to regulate miRNAs’ function in cancer cells.
format article
author Menghui Yin
Meidie Cheng
Chengli Liu
Keli Wu
Wei Xiong
Ji Fang
Yinxiong Li
Biliang Zhang
author_facet Menghui Yin
Meidie Cheng
Chengli Liu
Keli Wu
Wei Xiong
Ji Fang
Yinxiong Li
Biliang Zhang
author_sort Menghui Yin
title HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6
title_short HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6
title_full HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6
title_fullStr HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6
title_full_unstemmed HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6
title_sort hnrnpa2b1 as a trigger of rna switch modulates the mirna-mediated regulation of cdk6
publisher Elsevier
publishDate 2021
url https://doaj.org/article/8faa0f143d804ab5b62bfd656793089d
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