Recently Evolved Tumor Suppressor Transcript TP73-AS1 Functions as Sponge of Human-Specific miR-941.
Recently Evolved Tumor Suppressor Transcript TP73-AS1 Functions as Sponge of Human-Specific miR-941.
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最近进化的肿瘤抑制转录物 TP73-AS1 充当人类特异性 miR-941 的海绵
DOI：
10.1093/molbev/msy022
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发表时间：
2018-05-01
影响因子：
10.7
通讯作者：
Khaitovich P
中科院分区：
文献类型：
--
作者：
Hu H;Liu JM;Hu Z;Jiang X;Yang X;Li J;Zhang Y;Yu H;Khaitovich P
miRNA海绵是转录后基因调控的重要组成部分。然而，只有有限数量的miRNA海绵被鉴定出来。在这里，我们展示了最近进化的非编码肿瘤抑制转录物，TP73基因反义RNA (TP73‐AS1)，作为人类特异性miRNA miR‐941的天然海绵。我们在TP73‐AS1上发现了9个高亲和力的miR‐941结合位点聚集在1 kb区域内，形成了miR‐941海绵区。该海绵区域仅在人类中显示出增加的序列约束，其形成可以追溯到旧大陆猴子中包含单个miR - 941结合位点的71 nt长序列的串联扩增。基于大量转录组数据分析、伤口愈合实验和细胞系Argonaute蛋白免疫沉淀实验，我们进一步证实了TP73‐AS1作为高效miR‐941海绵的功能。miR - 941及其海绵的表达在多种健康和癌组织中呈负相关，miR - 941在肿瘤中高表达，并优先抑制肿瘤抑制因子。因此，TP73‐AS1和miR‐941二人组代表了控制细胞迁移、增殖和肿瘤发生的非编码调节因子极快进化的一个不寻常的案例。
Abstract MicroRNA (miRNA) sponges are vital components of posttranscriptional gene regulation. Yet, only a limited number of miRNA sponges have been identified. Here, we show that the recently evolved noncoding tumor suppressor transcript, antisense RNA to TP73 gene (TP73‐AS1), functions as a natural sponge of human‐specific miRNA miR‐941. We find unusually nine high‐affinity miR‐941 binding sites clustering within 1 kb region on TP73‐AS1, which forms miR‐941 sponge region. This sponge region displays increased sequence constraint only in humans, and its formation can be traced to the tandem expansion of a 71‐nt‐long sequence containing a single miR‐941 binding site in old world monkeys. We further confirm TP73‐AS1 functions as an efficient miR‐941 sponge based on massive transcriptome data analyses, wound‐healing assay, and Argonaute protein immunoprecipitation experiments conducted in cell lines. The expression of miR‐941 and its sponge correlate inversely across multiple healthy and cancerous tissues, with miR‐941 being highly expressed in tumors and preferentially repressing tumor suppressors. Thus, the TP73‐AS1 and miR‐941 duo represents an unusual case of the extremely rapid evolution of noncoding regulators controlling cell migration, proliferation, and tumorigenesis.
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影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
4.4
作者：
Hu HY;He L;Khaitovich P
通讯作者：
Khaitovich P
灵长类动物特异性长非编码 RNA 和 MicroRNA
DOI：
10.1016/j.gpb.2017.04.002
发表时间：
2017-06
期刊：
Genomics, proteomics & bioinformatics
影响因子：
--
作者：
Awan HM;Shah A;Rashid F;Shan G
通讯作者：
Shan G
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
8.8
作者：
Hezroni H;Koppstein D;Schwartz MG;Avrutin A;Bartel DP;Ulitsky I
通讯作者：
Ulitsky I