Alternate transcription of the Toll-like receptor signaling cascade

Wells, CA, Chalk, AM, Forrest, A, Taylor, D, Waddell, N, Schroder, K, Himes, SR, Faulkner, G, Lo, S, Kasukawa, T, Kawaji, H, Kai, C, Kawai, J, Katayama, S, Carninci, P, Hayashizaki, Y, Hume, DA and Grimmond, SM (2006) Alternate transcription of the Toll-like receptor signaling cascade. Genome Biology, 7 2: R10.1-R10.17.


Author Wells, CA
Chalk, AM
Forrest, A
Taylor, D
Waddell, N
Schroder, K
Himes, SR
Faulkner, G
Lo, S
Kasukawa, T
Kawaji, H
Kai, C
Kawai, J
Katayama, S
Carninci, P
Hayashizaki, Y
Hume, DA
Grimmond, SM
Title Alternate transcription of the Toll-like receptor signaling cascade
Journal name Genome Biology  (ERA 2012 Listed)    (ERA 2010 Rank A)
Publication date 2006-02-17
Sub-type Article
DOI 10.1186/gb-2006-7-2-r10
Volume number 7
Issue number 2
ISSN 1474-760X; 1465-6914; 1474-7596;
Start page R10.1
End page R10.17
Total pages 17
Place of publication London, U.K.
Publisher BioMed Central
Collection year 2006
Language eng
Subject C1
270201 Gene Expression
780105 Biological sciences
Formatted abstract Background: Alternate splicing of key signaling molecules in the Toll-like receptor (Tlr) cascade has been shown to dramatically alter the signaling capacity of inflammatory cells, but it is not known how common this mechanism is. We provide transcriptional evidence of widespread alternate splicing in the Toll-like receptor signaling pathway, derived from a systematic analysis of the FANTOM3 mouse data set. Functional annotation of variant proteins was assessed in light of inflammatory signaling in mouse primary macrophages, and the expression of each variant transcript was assessed by splicing arrays.

Results: A total of 256 variant transcripts were identified, including novel variants of Tlr4, Ticam1, Tollip, Rac1, Irak1, 2 and 4, Mapk14/p38, Atf2 and Stat1. The expression of variant transcripts was assessed using custom-designed splicing arrays. We functionally tested the expression of Tlr4 transcripts under a range of cytokine conditions via northern and quantitative real-time polymerase chain reaction. The effects of variant Mapk14/p38 protein expression on macrophage survival were demonstrated.

Conclusion: Members of the Toll-like receptor signaling pathway are highly alternatively spliced, producing a large number of novel proteins with the potential to functionally alter inflammatory outcomes. These variants are expressed in primary mouse macrophages in response to inflammatory mediators such as interferon-γ and lipopolysaccharide. Our data suggest a surprisingly common role for variant proteins in diversification/repression of inflammatory signaling.
Keyword Gene transcription
Toll-like receptor
Signalling cascade
I interferon receptor
Negative regulation
Splice variant
Gene encodes
Short-form
Proteins
Isoforms
Activation
Pathway
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 08:24:21 EST