Figure 3.

Translation regulation by a fungal thiamin pyrophosphate (TPP) riboswitch that controls alternative splicing. (A) Schematic representation of the region of the Neurospora crassa NMT1 pre–messenger RNA (mRNA) region that includes an intron and TPP riboswitch. The TPP aptamer (including stems P1 through P5) is stabilized on the binding ligand as depicted, or nucleotides from the P4 and P5 region can alternatively base-pair to a region encompassing a 5′SS. (B) Results of mRNA splicing when the TPP concentration is low. The alternative base-pairing depicted in A will sequester the proximal 5′SS to promote the use of a distal 5′SS. This produces a short mRNA splicing product wherein the main NMT1 open reading frame (ORF) can be translated. (C) TPP binding to the aptamer prevents occlusion of the proximal 5′SS, which results in a longer mRNA splicing product. This alternatively spliced RNA carries upstream ORFs (uORFs) that are translated instead of the main NMT1 ORF.