Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, pr. Lavrentieva 8, 630090 Novosibirsk, Russia.
Biochemistry (Mosc). 2012 May;77(5):425-34. doi: 10.1134/S0006297912050021.
Aquaporins (AQPs) belong to a transmembrane protein family of water channels that are permeable to water by the osmotic gradient. There are two isoforms of mouse AQP4 - M1 and M23. Their balance in the cell determines water permeability of the plasma membrane. These two isoforms are encoded by three mRNAs: M1 isoform is encoded by M1 mRNA and M23 isoform is encoded by M23 and M23X mRNAs. Here we found a new fourth mRNA of mouse AQP4 - M23A mRNA. The start of transcription is different for M23A mRNA from all the known AQP4 mRNAs. The 5'-untranslated region (5'-UTR) of M23A mRNA is encoded by four new exons (A, B, C, and D), which are located in the 5' region from exon-0 of the AQP4 gene. Alternative splicing between the exons-A, -B, -C, and -D leads to formation of multiple variants of M23A mRNA. We cloned six of these variants, all of which code full length M23 isoform of AQP4. Using RT-PCR we detected tissue-specific expression of the new M23A and already known M23, M23X, and M1 mRNAs. The M23A mRNA is expressed mostly in kidney, liver, and brain. Analysis of mRNA 5'-UTR structure showed low translation efficacy for M1 mRNA in comparison with high translation efficacy for M23A, M23X, and M23 mRNAs. We propose that AQP4 expression is controlled tissue-specifically by independent promoters. Thus multiple AQP4 mRNAs may allow long-term regulation of the balance between M1 and M23 AQP4 isoforms in the cell and thus water permeability of the plasma membrane.
水通道蛋白（AQP）属于跨膜蛋白家族的水通道，可通过渗透梯度通透水。鼠 AQP4 有两种同工型 - M1 和 M23。它们在细胞中的平衡决定了质膜的水通透性。这两种同工型由三种 mRNA 编码：M1 同工型由 M1 mRNA 编码，M23 同工型由 M23 和 M23X mRNA 编码。在这里，我们发现了鼠 AQP4 的一种新的第四种 mRNA - M23A mRNA。M23A mRNA 的转录起始与所有已知的 AQP4 mRNA 不同。M23A mRNA 的 5'-非翻译区（5'-UTR）由四个新的外显子（A、B、C 和 D）编码，这些外显子位于 AQP4 基因的外显子 0 区的 5'区域。外显子-A、-B、-C 和 -D 之间的选择性剪接导致 M23A mRNA 形成多种变体。我们克隆了其中的六种变体，它们都编码全长 M23 同工型 AQP4。使用 RT-PCR 我们检测到新的 M23A 和已经知道的 M23、M23X 和 M1 mRNA 在组织中的特异性表达。M23A mRNA 主要在肾脏、肝脏和大脑中表达。对 mRNA 5'-UTR 结构的分析表明，与高翻译效率的 M23A、M23X 和 M23 mRNA 相比，M1 mRNA 的翻译效率较低。我们提出 AQP4 的表达是由独立的启动子特异性控制的。因此，多种 AQP4 mRNA 可能允许细胞中 M1 和 M23 AQP4 同工型之间的平衡进行长期调节，从而调节质膜的水通透性。
