Pulmonary Surfactant-associated Protein A1 - Gene Regulation

Gene Regulation

Gene expression of SFTPA1 is regulated at different levels including gene transcription, post-transcriptional processing, stability and translation (biology) of mature mRNA. One of the important features of human surfactant protein A mRNAs is that they have a variable five prime untranslated region (5’UTR) generated from splicing variation of exons A, B, C, and D. At least 10 forms of human SFTPA1 and SFTPA2 5’UTRs have been identified that differ in nucleotide sequence, length, and relative amount. Specific SFTPA1 or SFTPA2 5’UTRs have also been characterized. Some SFTPA1 specific 5’UTRs include exons B’ or C. These two exons contain upstream AUGs (uAUGs) that can potentially act as sites for translation initiation (see eukaryotic translation), affecting protein translation and SFTPA1 relative content. The majority of SFTPA1 transcripts lack exon B, a sequence implicated in transcription and translation enhancement, indicating a differential regulation of SFTPA1 and SFTPA2 expression. The AD’ form is the most represented among SFTPA1 transcripts (81%), and experimental work has shown that this sequence can stabilize mRNA and enhance translation, but the mechanisms implicated in this regulation are still under investigation. While differences at the 5’UTR are shown to regulate both transcription and translation, polymorphisms at the 3’UTR of SP-A1 variants are shown to primarily, differentially affect translation efficiency via mechanisms that involve binding of proteins and/or . The impact of this regulation on SFTPA1 and SFTPA2 protein levels may contribute to individual differences in susceptibility to lung disease. Environmental insults and pollutants also affect SFTPA1 expression. Exposure of lung cells to particulate matter affects splicing of 5’UTR exons of SFTPA1 transcripts. Pollutants and viral infections also affect SFTPA1 translation mechanisms (see eukaryotic translation, translation (biology)).