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	Alternate transcription of the Toll-like receptor signalling cascade. Christine A Wells1,2Alistair Chalk1,3, Alistair Forrest2, Darrin Taylor2, Nic Waddell2, Kate Schroder2, S. Roy Himes2, Geoffrey Faulkner2, Sandra Lo1, Takeya Kasukawa4, Hideya Kawaji4, Chikatoshi Kai4, Jun Kawai4,5, Shintaro Katayama4, Piero Carninci4 , Yoshihide Hayashizaki4, David A Hume2, and Sean M Grimmond2 1. Eskitis Institute for Cell and Molecular Therapies, School of Biological and Biomedical Sciences, Griffith University, Brisbane, Australia Corresponding author. 2. The Institute for Molecular Biosciences, The University of QLD, Brisbane, Australia 3. Karolinska Institutet, Sweden 4. Genome Exploration Research Group (Genome Network Project Core Group), RIKEN Genomic Sciences Center (GSC), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan. 5. Genome Science Laboratory, Discovery Research Institute, RIKEN Wako Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan Status: Submitted Abstract: Alternate splicing of key signalling molecules in the Tlr cascade has been shown to dramatically alter the signalling capacity of inflammatory cells, but it is not known how widespread this mechanism is. The FANTOM3 dataset provided unprecedented insights into the transcriptional complexity of the mouse genome, and was used to systematically analyse alternate transcription of the Toll-like receptor pathways. Two hundred and fifty six variant transcripts were identified, and validated using custom-designed splicing arrays. We describe novel variants of each step in the Tlr cascade including novel variants of Tlr4, Ticam1, Tollip, Rac1, Irak1, 2 and 4, Mapk14/p38, Atf2 and Stat1. Our data suggest a surprisingly common role for variant proteins in diversification/repression of inflammatory signalling. The following provides links to genes in the mouse TLR pathway and others likely to be associated with inflammatory response. Links are provided to a 3-frame window browser: Frame 1: Table of all individual transcripts generated from these loci, interpro predictions, coding potential. Frame 2: A genomic view of the locus. Frame 3: An optional transcript centric view showing the transcript in the FANTOM3 MATRICS viewer with peptide predictions and alignments mapped to the sequence. All predictions and processing are GFF files that are mapped to the mouse genome using the FANTOM genome browser. To view the domain predictions you must first load the following gff files into the FANTOM genome browser (technical constraints prevent us from pre-loading this data for you) Open the FANTOM genome browser by clicking here. In the "Upload your own annotations" section, upload the following files: File containing full prediction information about the domains. download File containing the splice junctions. download A file containing data on macrophage Tag Clusters download A file containing data the cds start and stop for each PA.X download(updated) Note that this file only shows start-end, not use of exons. You can then click on the links below to find your gene of interest. Toll-like receptor signaling pathway - Mus musculus used with permission of the Kyoto Encyclopedia of Genes and Genomes (KEGG) TK List - linked to database browser Stat1 (TA100600.1) Stat1 (TA100600.2) Stat1 (TA100600.3) Stat1 (TA100600.4) Stat1 (TA100600.5) Stat1 (TA100600.6) Serpinb3b (TA100817.1) Pik3cb (TA100817.2) Pik3cb (TA100817.3) Myst1 (TA101855.1) Myst1 (TA101855.2) Myst1 (TA101855.3) na (TA102412.1) Cxcl11 (TA103415.1) Cxcl11 (TA103415.2) Ly96 (TA104041.1) Fadd (TA104301.1) Tlr4 (TA104448.1) Tlr4 (TA104448.2) Sema3d (TA104574.1) Akt2 (TA104574.2) Akt2 (TA104574.3) Akt2 (TA104574.4) Peli2 (TA104834.1) Peli2 (TA104834.2) Peli2 (TA104834.3) Peli2 (TA104834.4) Trib2 (TA105143.1) Map2k4 (TA105143.2) Irf2 (TA105438.1) Irf2 (TA105438.2) Irf2 (TA105438.3) 6330509M05Rik (TA105610.1) Mapk9 (TA105610.2) Mapk9 (TA105610.3) Mapk9 (TA105610.4) Ikbke (TA105751.1) Ikbke (TA105751.2) Ikbke (TA105751.3) Mapk14 (TA106167.1) Mapk14 (TA106167.2) Syt2 (TA106311.1) Tlr7 (TA106311.2) Tlr7 (TA106311.3) Tlr7 (TA106311.4) Clecsf9 (TA106323.1) Clecsf9 (TA106323.2) 9930031P18Rik (TA106356.1) Myst3 (TA106356.2) Myst3 (TA106356.3) 5830468K18Rik (TA106367.1) Hdac3 (TA106367.2) Fli1 (TA106548.1) Mapkap1 (TA106548.2) Mapkap1 (TA106548.3) Mapkap1 (TA106548.4) Mapkap1 (TA106548.5) Pik3cd (TA106669.1) Pik3cd (TA106669.2) Pik3cd (TA106669.3) Pik3cd (TA106669.4) Pik3cd (TA106669.5) Pik3cd (TA106669.6) Pik3cd (TA106669.7) Cxcl9 (TA106717.1) Tbk1 (TA107464.1) Tbk1 (TA107464.2) 9530037G02Rik (TA107567.1) C130045F17Rik (TA108218.1) Ifnar2 (TA108218.2) Ifnar2 (TA108218.3) Ifnar2 (TA108218.4) 6230425F05Rik (TA108426.1) Stat3 (TA108426.2) Stat3 (TA108426.3) Stat3 (TA108426.4) Tlr3 (TA109507.1) Tlr3 (TA109507.2) Tlr3 (TA109507.3) Cd86 (TA109555.1) Cd86 (TA109555.2) Apip (TA109625.1) Map2k6 (TA109625.2) Map2k6 (TA109625.3) Map2k6 (TA109625.4) Pde4a (TA109796.1) Pde4a (TA109796.2) Pik3r5 (TA109796.3) 2310010G13Rik (TA109806.1) Rela (TA109806.2) Rela (TA109806.3) Rela (TA109806.4) Rela (TA109806.5) Cd80 (TA110802.1) Cd80 (TA110802.2) Cd80 (TA110802.3) Cd80 (TA110802.4) Leftb (TA110910.1) Casp8 (TA110910.2) Fos (TA111589.1) Nfkbia (TA111714.1) Il6 (TA111842.1) Pfc (TA112049.1) Cd14 (TA112049.2) Cd14 (TA112049.3) Apod (TA112090.1) Irak4 (TA121381.1) Irak4 (TA121381.2) Irak4 (TA121381.3) na (TA127777.1) Zfp457 (TA131489.1) Sumo2 (TA131489.2) Sumo2 (TA131489.3) Sumo2 (TA131489.4) Sumo2 (TA131489.5) Dnmt1 (TA134148.1) Dnmt1 (TA134148.2) Dnmt1 (TA134148.3) Dnmt1 (TA134148.4) Dnmt1 (TA134148.5) Dnmt1 (TA134148.6) Tollip (TA151087.1) Traf6 (TA151150.1) Bcl9 (TA157808.1) Bcl9 (TA157808.10) Mapk8ip3 (TA157808.2) Mapk8ip3 (TA157808.3) Mapk8ip3 (TA157808.4) Mapk8ip3 (TA157808.5) Mapk8ip3 (TA157808.6) Mapk8ip3 (TA157808.7) Mapk8ip3 (TA157808.8) Mapk8ip3 (TA157808.9) Rps18 (TA161134.1) Irf1 (TA161134.2) Irf1 (TA161134.3) Atf2 (TA165927.1) Atf2 (TA165927.2) Map2k3 (TA168130.1) Map2k3 (TA168130.2) Hat1 (TA168238.1) Hat1 (TA168238.2) 2900054C01Rik (TA168363.1) Mapk1 (TA168363.2) Arhgef2 (TA174048.1) Hdac6 (TA174048.2) Hdac6 (TA174048.3) D930005D10Rik (TA177219.1) Ifnar1 (TA177219.2) Ifnar1 (TA177219.3) Ifnar1 (TA177219.4) Ccl3 (TA177314.1) 2900057H02Rik (TA181931.1) Irak2 (TA181931.2) Irak2 (TA181931.3) Irak2 (TA181931.4) Irak2 (TA181931.5) Rac3 (TA221928.1) Mapk11 (TA222045.1) Atp6v1e2 (TA222079.1) Atp6v1e2 (TA222079.2) E230008O15Rik (TA227080.1) E430034L04Rik (TA227080.2) E430034L04Rik (TA227080.3) E430034L04Rik (TA227080.4) E430034L04Rik (TA227080.5) Cxcl10 (TA227083.1) Msx1 (TA227085.1) Tlr1 (TA227085.2) Tlr1 (TA227085.3) Sin3a (TA227196.1) Sin3a (TA227196.2) Sin3a (TA227196.3) Sin3a (TA227196.4) Sin3a (TA227196.5) Map3k1 (TA6330.1) Map3k7 (TA6337.1) Pik3c2g (TA71447.1) Pik3c2g (TA71447.2) Tlr9 (TA71667.1) Irak1 (TA71769.1) Irak1 (TA71769.2) Sumo1 (TA71937.1) Mapk8ip1 (TA72039.1) Mapk8ip1 (TA72039.2) Mapk8ip1 (TA72039.3) Mapk8ip1 (TA72039.4) Mapk8ip1 (TA72039.5) Ccl5 (TA72101.1) Ikbkb (TA72220.1) Ikbkb (TA72220.2) Akt3 (TA72372.1) Akt3 (TA72372.2) Tlr2 (TA72378.1) Il12a (TA72395.1) Il12a (TA72395.2) Il12b (TA72396.1) Il12b (TA72396.2) Il12b (TA72396.3) Il12b (TA72396.4) Il12b (TA72396.5) Il12b (TA72396.6) Ccl4 (TA72398.1) Nfkb2 (TA72514.1) Nfkb2 (TA72514.2) Nfkb2 (TA72514.3) Myst4 (TA72778.1) Tlr6 (TA73054.1) Tlr6 (TA73054.2) Ikbkg (TA73458.1) Ikbkg (TA73458.2) Lbp (TA73552.1) Pik3cg (TA73626.1) Pik3cg (TA73626.2) Map3k7ip1 (TA74186.1) Map3k7ip2 (TA74418.1) Mif (TA75653.1) Irf3 (TA76746.1) Irf3 (TA76746.2) Chuk (TA77541.1) Chuk (TA77541.2) Mapk8 (TA79202.1) Pik3c3 (TA79647.1) Pik3c3 (TA79647.2) Nfkb1 (TA79889.1) Nfkb1 (TA79889.2) Nfkb1 (TA79889.3) Nfkb1 (TA79889.4) Pik3c2a (TA79973.1) Pik3c2a (TA79973.2) Mapk12 (TA81462.1) Mapk12 (TA81462.2) Myd88 (TA81611.1) Pik3r1 (TA82198.1) Pik3r1 (TA82198.2) Pik3r1 (TA82198.3) Pik3r1 (TA82198.4) Myst2 (TA82580.1) Myst2 (TA82580.2) Tnf (TA83001.1) Il1b (TA83017.1) Pik3ca (TA83188.1) Stat4 (TA83197.1) Hdac2 (TA83253.1) Atm (TA83287.1) Atm (TA83287.2) Mapk13 (TA83366.1) Tnfsf5 (TA83476.1) Pik3r2 (TA83569.1) Pik3r2 (TA83569.2) Clecsf12 (TA83814.1) Clecsf12 (TA83814.2) Ticam2 (TA84178.1) Ticam2 (TA84178.2) Ticam2 (TA84178.3) Ifnb1 (TA84372.1) 1110011C06Rik (TA98057.1) Stat2 (TA98057.2) Stat2 (TA98057.3) Tirap (TA107567) Tlr5 (TA79009.1) Trif (TA222079.6) Pathway steps with multiple genes Nfkb1 Nfkb2 Rela Akt1 Akt2 Akt3 Map2k3 Map2k6 Ifna2 Ifna4 Ifna5 Ifna6 Ifna7 Ifna9 Ifnab Ifna11 Ifna13 LOC242517 Ifna12 LOC384100 Ifna14 Pik3c2a Pik3c2g Pik3ca Pik3cd Pik3c1 Pik3c2 Pik3c3 Pik3cg Pik3r5 Pik3cb Pik3r4 Fos Jun Mapk11 Mapk12 Mapk13 Mapk14 Il12a Il12b Rac1 Rac2 Rac3 Ifnar1 Ifnar2 Mapk8 Mapk9 Keywords: Toll-like receptors, innate immunity, alternate splicing, signal transduction, inflammation