An RNA structure-mediated post-transcriptional model of a-1-antitrypsin deficiency

Six transcripts of the gene SERPINA1 (serpin family A member 1) were sequenced via SHAPE-MaP to obtain their secondary structure profiles. For each transcript, SHAPE-MaP includes a sample treated with 1M7 reagent (''p''), a minus reagent negative control (''m''), and a denatured control (''d''). The 1M7 reagent preferentially reacts with unpaired bases in RNA and subsequently induces mutations during the reverse transcription step of library preparation. After sequencing and alignment, the ''mutational profiles'' of the ''p'', ''d'' and ''m'' samples are used to calculate the SHAPE reactivity of each base in the transcript. SHAPE reactivity correlates to the tendency of a base to be paired as part of a secondary structure. Overall design: Transcript-specific SHAPE-MaP on six SERPINA1 transcripts.