Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effect of SF3A1 inhibition on pre-mRNA splicing

ABSTRACT: We previously found that the SF3A mRNA splicing complex was required for a robust innate immune response; SF3A acts in part by inhibiting the production of a negatively acting splice form of the TLR signaling adaptor MyD88. Here we inhibit SF3A1 using RNAi and subsequently perform an RNAseq study to identify the full complement of genes and splicing events regulated by SF3A in murine macrophages. Surprisingly, SF3A has substantial specificity for mRNA splicing events in innate immune signaling pathways compared to other pathways, affecting the splicing of many genes in the TLR signaling pathway to modulate the innate immune response. RNAseq was used to monitor the effects of SF3A1 siRNA-mediated knockdown in murine macrophages. Three biological replicates were used for each of the four treatment combinations (with/without siRNA, with/without LPS). The first replicates for each combination were each sequenced in two runs, which were combined in the analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Scott Alper 

PROVIDER: E-GEOD-58432 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex.

O'Connor Brian P BP   Danhorn Thomas T   De Arras Lesly L   Flatley Brenna R BR   Marcus Roland A RA   Farias-Hesson Eveline E   Leach Sonia M SM   Alper Scott S  

PLoS genetics 20150206 2

The innate immune response plays a key role in fighting infection by activating inflammation and stimulating the adaptive immune response. However, chronic activation of innate immunity can contribute to the pathogenesis of many diseases with an inflammatory component. Thus, various negatively acting factors turn off innate immunity subsequent to its activation to ensure that inflammation is self-limiting and to prevent inflammatory disease. These negatively acting pathways include the productio  ...[more]

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