Limiting of the innate immune response by SF3A-dependent control of MyD88 alternative mRNA splicing.

Abstract:

:Controlling infectious disease without inducing unwanted inflammatory disease requires proper regulation of the innate immune response. Thus, innate immunity needs to be activated when needed during an infection, but must be limited to prevent damage. To accomplish this, negative regulators of innate immunity limit the response. Here we investigate one such negative regulator encoded by an alternative splice form of MyD88. MyD88 mRNA exists in two alternative splice forms: MyD88L, a long form that encodes a protein that activates innate immunity by transducing Toll-like receptor (TLR) signals; and a short form that encodes a different protein, MyD88S, that inhibits the response. We find that MyD88S levels regulate the extent of inflammatory cytokine production in murine macrophages. MyD88S mRNA levels are regulated by the SF3A and SF3B mRNA splicing complexes, and these mRNA splicing complexes function with TLR signaling to regulate MyD88S production. Thus, the SF3A mRNA splicing complex controls production of a negative regulator of TLR signaling that limits the extent of innate immune activation.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

De Arras L,Alper S

doi

10.1371/journal.pgen.1003855

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

e1003855

issue

10

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-13-00209

journal_volume

9

pub_type

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