Plasmacytoid dendritic cells and granulocytes were depleted in vivo by intravenous injection of 100 mg anti-mPDCA-1 mAb (clone JF05-1C2.4.1, functional grade; Miltenyi Biotec) or 10 mg anti-Gr1 mAb (clone RB6-8C5) 24 hours prior Listeria monocytogenes infection. As an isotype control, rat IgG (Jackson ImmunoResearch Laboratories, Inc.) was used. Successful depletion of pDCs and granulocytes was determined by FACS analysis 24 hours after infection. Figure S1 Overview of transgenic mice used in this work. The generation of the global IFN-b reporter mouse has been previously described [30] and is since then maintained independent of cre expression. In brief, the targeted locus contains a luciferase gene (dark blue arrow) with a preceding polyA signal (black box) to avoid unspecific reporter activity. Two loxP sites (black arrowheads) allow cre-dependent replacement of the ifnb coding sequence by the luciferase reporter (light blue arrow) which is then driven by the endogenous ifnb promoter. In all reporter mice we keep one wt ifnb allel to allow IFN-b expression. Tissue specific reporter mice were obtained from breeding IFN-b floxb-luc/floxb-luc mice with mice expressing cre (red arrow) in a cell type specific manner. Cre activity (light red) in the given cell population (within the red circle) then allows ifnb promoter dependent reporter activity while the reporter cannot be activated in cells without cre expression (dark red). Tissue specific knockout mice carry two cre dependent alleles. Therefore in cells expressing cre both ifnb coding sequences are deleted. However, in cells without cre expression the IFN-b production is normal despite the genomic alterations introduced into the locus.  Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast Although first discovered in viruses, previous studies have identified operational −1 ribosomal frameshifting (−1 RF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. Here, four yeast −1 RF signals are shown to promote significant mRNA destabilization through the nonsense mediated mRNA decay pathway (NMD), and genetic evidence is presented suggesting that they may also operate through the no-go decay pathway (NGD) as well. Yeast EST2 mRNA is highly unstable and contains up to five −1 RF signals. Ablation of the −1 RF signals or of NMD stabilizes this mRNA, and changes in −1 RF efficiency have opposing effects on the steady-state abundance of the EST2 mRNA. These results demonstrate that endogenous −1 RF signals function as mRNA destabilizing elements through at least two molecular pathways in yeast. Consistent with current evolutionary theory, phylogenetic analyses suggest that −1 RF signals are rapidly evolving cis-acting regulatory elements. Identification of high confidence −1 RF signals in ∼10% of genes in all eukaryotic genomes surveyed suggests that −1 RF is a broadly used post-transcriptional regulator of gene expression. Programmed ribosomal frameshifting (PRF) is has historically been associated with the study of viruses. PRF signals stochastically redirect ribosomes into new reading frames and viral PRF promotes synthesis of C-terminally extended fusion proteins. The most well defined PRF signals direct ribosomes to slip by one nucleotide in the 5 0 (À1) direction. À1 PRF signals typically contain three elements: a 'slippery site' composed of seven nucleotides (X XXY YYZ, incoming zero-frame indicated by spaces) where shifting occurs; a short spacer sequence and a downstream stimulatory structure, typically an mRNA pseudoknot (1) (2) (3) . Current models posit that the pseudoknot directs ribosomes to pause with their aminoacyl-(aa-) and peptidyl-tRNAs positioned over the slippery sequence, where re-pairing of the non-wobble bases of both tRNAs with the À1 frame codons occurs (4) (5) (6) (7) .