Fig. 1.

a Regulation of APP expression, mediated through its 3′UTR, is influenced by several miRNA-binding sites, cis-acting regulatory elements and binding proteins, and single-nucleotide polymorphisms (SNPs). The human APP 3′UTR is ~1,120 nucleotides long. The alternative polyadenylation site leading to a shorter APP transcript is indicated by a broken line. The location of validated miRNA-binding sites are shown throughout the length of the shorter APP 3′UTR. SNPs that have been identified in AD and also overlap with miRNA-binding sites are indicated in red. The location of the three regulatory elements bound by various proteins which function to stabilize/destabilize APP mRNA is indicated. PAI/RBP1 plasminogen activator inhibitor-RNA binding protein 1, YB1 Y-box binding protein 1, La/SS-B autoantigen La/Sjögren syndrome antigen B, EF1α elongation factor 1a, hnRNPC heterogeneous nuclear ribonucleoprotein C. b ncRNA regulation of BACE1. BACE1-AS binds to and stabilizes BACE1 mRNA through complementarity with exon 6. The BACE1 mRNA is targeted by several miRNAs, predominantly through its 3′UTR but also via exon 6. The miR-29 family has two predicted binding sites, however, miR-29c only exerts repression through the first site and not the second. This has not been tested for the family members miR-29a and miR-29b-1