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MROH7-TTC4 通读长非编码 RNA 抑制血管内皮细胞凋亡,并通过抑制 ANXA7 GTP 酶活性而上调。

MROH7-TTC4 read-through lncRNA suppresses vascular endothelial cell apoptosis and is upregulated by inhibition of ANXA7 GTPase activity.

机构信息

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, China.

Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.

出版信息

FEBS J. 2019 Dec;286(24):4937-4950. doi: 10.1111/febs.15038. Epub 2019 Aug 24.

Abstract

Apoptosis of vascular endothelial cells (VEC) is the main form of vascular injury that is closely linked to numerous cardiovascular diseases. Therefore, it is important to find new factors that can suppress VEC apoptosis. By using long noncoding RNA (lncRNA) microarray analysis, we found a new read-through lncRNA, MROH7-TTC4, which acted as an apoptosis inhibitor in VECs. Furthermore, by using the inhibitor (ABO) of annexin A7 (ANXA7) GTPase, we discovered that ANXA7 translocated into nucleus and interacted with 5'→3' exoribonuclease (XRN2). The decreased XRN2 phosphorylation induced by ANXA7 GTPase activity inhibition, promoted MROH7-TTC4 expression. Moreover, T-cell intracellular antigen-1 (TIA1), a binding protein of MROH7-TTC4, processed it into MROH7 and TTC4 that could inhibit VEC apoptosis. Here, we conclude that inhibiting ANXA7 GTPase activity promotes the interaction of ANXA7 and XRN2 in nucleus, which regulates the read-through transcription of MROH7-TTC4, and TIA1 is responsible for the process of MROH7-TTC4 that inhibits apoptosis through MROH7 and TTC4.

摘要

血管内皮细胞(VEC)的凋亡是与许多心血管疾病密切相关的主要血管损伤形式。因此,寻找新的能够抑制 VEC 凋亡的因素非常重要。通过使用长链非编码 RNA(lncRNA)微阵列分析,我们发现了一种新的读通 lncRNA,MROH7-TTC4,它在 VEC 中作为一种凋亡抑制剂发挥作用。此外,通过使用膜联蛋白 A7(ANXA7)GTP 酶的抑制剂(ABO),我们发现 ANXA7 易位到核内并与 5'→3'外切核酸酶(XRN2)相互作用。ANXA7 GTP 酶活性抑制诱导的 XRN2 磷酸化减少,促进 MROH7-TTC4 的表达。此外,T 细胞内抗原-1(TIA1),是 MROH7-TTC4 的结合蛋白,将其加工成 MROH7 和 TTC4,这可以抑制 VEC 凋亡。在这里,我们得出结论,抑制 ANXA7 GTP 酶活性促进了核内 ANXA7 和 XRN2 的相互作用,从而调节 MROH7-TTC4 的读通转录,而 TIA1 负责通过 MROH7 和 TTC4 抑制凋亡的 MROH7-TTC4 的加工。

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