ILF3

This gene encodes a double-stranded RNA (dsRNA) binding protein that complexes with other proteins, dsRNAs, small noncoding RNAs, and mRNAs to regulate gene expression and stabilize mRNAs. This protein (NF90, ILF3) forms a heterodimer with a 45 kDa transcription factor (NF45, ILF2) required for T-cell expression of interleukin 2. This complex has been shown to affect the redistribution of nuclear mRNA to the cytoplasm. Knockdown of NF45 or NF90 protein retards cell growth, possibly by inhibition of mRNA stabilization. In contrast, an isoform (NF110) of this gene that is predominantly restricted to the nucleus has only minor effects on cell growth when its levels are reduced. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Full Name

interleukin enhancer binding factor 3

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.

Biological Process

Defense response to virusIEA:UniProtKB-KW
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of translationISS:UniProtKB
Negative regulation of viral genome replicationISS:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

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.

PTM

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.