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探索 mRNA 3'-UTR G-四联体:在可变多聚腺苷酸化和 mRNA 缩短中均有作用的证据。

Exploring mRNA 3'-UTR G-quadruplexes: evidence of roles in both alternative polyadenylation and mRNA shortening.

机构信息

RNA Group/Groupe ARN, Département de biochimie, Faculté de médecine et des sciences de santé, Pavillon de recherche appliquée au cancer, Université de Sherbrooke, QC J1E 4K8, Canada.

出版信息

Nucleic Acids Res. 2013 Jun;41(11):5898-911. doi: 10.1093/nar/gkt265. Epub 2013 Apr 22.

DOI:10.1093/nar/gkt265
PMID:23609544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3675481/
Abstract

Guanine-rich RNA sequences can fold into non-canonical, four stranded helical structures called G-quadruplexes that have been shown to be widely distributed within the mammalian transcriptome, as well as being key regulatory elements in various biological mechanisms. That said, their role within the 3'-untranslated region (UTR) of mRNA remains to be elucidated and appreciated. A bioinformatic analysis of the 3'-UTRs of mRNAs revealed enrichment in G-quadruplexes. To shed light on the role(s) of these structures, those found in the LRP5 and FXR1 genes were characterized both in vitro and in cellulo. The 3'-UTR G-quadruplexes were found to increase the efficiencies of alternative polyadenylation sites, leading to the expression of shorter transcripts and to possess the ability to interfere with the miRNA regulatory network of a specific mRNA. Clearly, G-quadruplexes located in the 3'-UTRs of mRNAs are cis-regulatory elements that have a significant impact on gene expression.

摘要

富含鸟嘌呤的 RNA 序列可以折叠成非 canonical 的四链螺旋结构,称为 G-四联体,已被证明广泛分布于哺乳动物转录组中,并且是各种生物学机制中的关键调节元件。也就是说,它们在 mRNA 的 3'-非翻译区 (UTR) 中的作用仍有待阐明和理解。对 mRNA 的 3'-UTRs 的生物信息学分析显示 G-四联体富集。为了阐明这些结构的作用,对 LRP5 和 FXR1 基因中的结构进行了体外和细胞内的表征。发现 3'-UTR G-四联体可以提高可变多聚腺苷酸化位点的效率,导致较短转录本的表达,并具有干扰特定 mRNA 的 miRNA 调节网络的能力。显然,位于 mRNA 3'-UTRs 中的 G-四联体是顺式调节元件,对基因表达有重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/6674833ddaf7/gkt265f4p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/737073c9332f/gkt265f1p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/896153ef64f0/gkt265f2p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/5e2e6793e34f/gkt265f3p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/6674833ddaf7/gkt265f4p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/737073c9332f/gkt265f1p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/896153ef64f0/gkt265f2p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/5e2e6793e34f/gkt265f3p.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f1c/3675481/6674833ddaf7/gkt265f4p.jpg

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