Department of Biochemistry, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
Int J Mol Sci. 2020 Sep 4;21(18):6460. doi: 10.3390/ijms21186460.
Mature mRNA is generated by the 3' end cleavage and polyadenylation of its precursor pre-mRNA. Eukaryotic genes frequently have multiple polyadenylation sites, resulting in mRNA isoforms with different 3'-UTR lengths that often encode different C-terminal amino acid sequences. It is well-known that this form of post-transcriptional modification, termed alternative polyadenylation, can affect mRNA stability, localization, translation, and nuclear export. We focus on the alternative polyadenylation of pre-mRNA for vascular endothelial growth factor receptor-1 (VEGFR-1), the receptor for VEGF. VEGFR-1 is a transmembrane protein with a tyrosine kinase in the intracellular region. Secreted forms of VEGFR-1 (sVEGFR-1) are also produced from the same gene by alternative polyadenylation, and sVEGFR-1 has a function opposite to that of VEGFR-1 because it acts as a decoy receptor for VEGF. However, the mechanism that regulates the production of sVEGFR-1 by alternative polyadenylation remains poorly understood. In this review, we introduce and discuss the mechanism of alternative polyadenylation of VEGFR-1 mediated by protein arginine methylation.
成熟的 mRNA 是由其前体 pre-mRNA 的 3' 端切割和多聚腺苷酸化产生的。真核基因通常具有多个多聚腺苷酸化位点，导致具有不同 3'UTR 长度的 mRNA 异构体，这些异构体通常编码不同的 C 末端氨基酸序列。众所周知，这种转录后修饰形式，称为可变多聚腺苷酸化，可以影响 mRNA 的稳定性、定位、翻译和核输出。我们专注于血管内皮生长因子受体-1（VEGFR-1）前体 mRNA 的可变多聚腺苷酸化，VEGFR-1 是 VEGF 的受体。VEGFR-1 是一种跨膜蛋白，其细胞内区域具有酪氨酸激酶。通过可变多聚腺苷酸化也从同一基因产生 VEGFR-1 的分泌形式（sVEGFR-1），并且 sVEGFR-1 具有与 VEGFR-1 相反的功能，因为它作为 VEGF 的诱饵受体发挥作用。然而，调节 sVEGFR-1 可变多聚腺苷酸化产生的机制仍知之甚少。在这篇综述中，我们介绍并讨论了由蛋白质精氨酸甲基化介导的 VEGFR-1 可变多聚腺苷酸化的机制。
