SFTPA2B - Gene Regulation

Gene Regulation

Gene expression of SFTPA2 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 SFTPA2 and SFTPA1 5’UTRs have been identified that differ in nucleotide sequence, length, and relative amount. Most SFTPA2 specific 5’UTRs include exon B. This 30-nucleotide long sequence has been shown to enhance both gene transcription and protein translation (biology), and plays a key role in the differential regulation of SFTPA2 and SFTPA1 expression. Both ABD and ABD’ are the most represented forms among SFTPA2 transcripts (~49% each), and experimental work has shown that this sequence can stabilize mRNA, enhance translation, and activate cap-independent eukaryotic translation. Exon B of SFTPA2 also binds specific proteins (e.g. 14-3-3) that may enhance translation, in a sequence- and secondary structure- specific way. While differences at the 5’UTR are shown to regulate both transcription and translation, polymorphisms at the 3’UTR of SP-A2 variants are shown to primarily, differentially affect translation efficiency via mechanisms that involve binding of proteins and/or . The impact of this regulation on SFTPA2 relative protein levels may contribute to individual differences in susceptibility to lung disease. Environmental insults and pollutants also affect SFTPA2 expression. Exposure of lung cells to particulate matter affects splicing of 5’UTR exons of SFTPA2 transcripts. Pollutants and viral infections also affect SFTPA2 translation mechanisms (see eukaryotic translation, translation (biology)).