Alternate transcription of the Toll-like receptor signaling cascade

Loading...
Thumbnail Image
File version
Author(s)
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
Primary Supervisor
Other Supervisors
Editor(s)
Date
2006
Size
718155 bytes
64072 bytes
File type(s)
application/pdf
text/plain
Location
License
http://creativecommons.org/licenses/by/2.0
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-gamma and lipopolysaccharide. Our data suggest a surprisingly common role for variant proteins in diversification/repression of inflammatory signaling.

Journal Title
Genome Biology
Conference Title
Book Title
Edition
Volume
7
Issue
Thesis Type
Degree Program
School
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
© 2006 Wells et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Item Access Status
Note
Page numbers are not for citation purposes. Instead, this article has the unique article number of R10.
Access the data
Related item(s)
Subject
Environmental sciences
Biological sciences
Information and computing sciences
Persistent link to this record
Citation
Collections