FIG. 2.

Integrated model for type I interferon (IFN) mRNA decay by KSRP and tristetraprolin (TTP) during the multistage induction. In non-infected cells, Ifnb and perhaps Ifna4 are expressed at very low levels. Constitutively expressed KSRP targets the mRNAs for decay. In the early phase of viral infection, activation of IFN regulatory factors, IRF3 and IRF7, leads to elevated expression of Ifnb, Ifna4, and Ttp. These induced Ifna4/b mRNAs are targeted for decay by both KSRP and TTP. In the late phase of viral infection, increased production of IFN-β and IFN-α4 acting in an autocrine and a paracrine fashion leads to a strong production of IRF7 by activated ISGF3. Activation of the newly synthesized IRF7 results in further amplification of Ifnb and other Ifna transcription. IFN-β induces STAT1-dependent Ttp transcription, in which Ifnb mRNA and perhaps mRNAs encoding other Ifna subtypes are subjected to decay by both TTP and KSRP.