ILF3
Function
RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs (PubMed:28625552). As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response (PubMed:21123651, PubMed:34110282). Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs (PubMed:21123651, PubMed:28625552).
(Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3.
Post-translational modifications
Phosphorylated at Thr-188 and Thr-315 by PKR in response to certain RNA viruses. This phosphorylation results in the dissociation of ILF2 from the ILF2-ILF3 complex resulting in a cytoplasmic sequestration of ILF3 where it can bind to viral RNAs and impede viral replication.
Methylated by protein arginine N-methyltransferase 1.
Ubiquitinated at Lys-297 in a TRIM47-dependent manner; this 'Lys-48'-linked ubiquitination promotes ILF3 degradation.
Tissue Specificity
Ubiquitous.
Cellular localization
- Nucleus
- Nucleolus
- Cytoplasm
- Nucleus
- Localizes in the cytoplasm in response to viral infection. The unphosphorylated form is retained in the nucleus by ILF2. Phosphorylation at Thr-188 and Thr-315 causes the dissociation of ILF2 from the ILF2-ILF3 complex resulting in a cytoplasmic sequestration of ILF3. Localized in cytoplasmic mRNP granules containing untranslated mRNAs.
Alternative names
DRBF, MPHOSPH4, NF90, ILF3, Interleukin enhancer-binding factor 3, Double-stranded RNA-binding protein 76, M-phase phosphoprotein 4, Nuclear factor associated with dsRNA, Nuclear factor of activated T-cells 90 kDa, Translational control protein 80, DRBP76, MPP4, NFAR, NF-AT-90, TCP80