2Karolinska Institutet, ALB KS, Q2:09, 17176 Stockholm, Sweden; fax: +468-517-77328; E-mail: email@example.com
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Received December 16, 2011; Revision received February 2, 2012
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.
KEY WORDS: aquaporin-4, mRNA, gene, exon, alternative splicing, mouse