An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein

TWEAK and APRIL are two recently identified tumour necrosis factor (TNF) ligand family members, implicated in angiogenesis and immune regulation, respectively. TWEAK is a transmembrane protein expressed on the cell surface, whereas APRIL acts solely as a secreted factor. In this report, using RACE, RT–PCR, cDNA library screening and an RNase protection assay, we characterize a hybrid transcript between TWEAK and APRIL mRNAs. The encoded TWE‐PRIL protein is composed of TWEAK cytoplasmic and transmembrane domains fused to the APRIL C‐terminal domain. TWE‐PRIL mRNA is expressed and translated in human primary T cells and monocytes, and endogenous TWE‐PRIL protein was detected in primary human T lymphocytes and monocytic cell lines. TWE‐PRIL is membrane anchored and presents the APRIL receptor‐binding domain at the cell surface. It is a biologically active ligand, as it stimulates cycling in T‐ and B‐lymphoma cell lines. Much like membrane‐bound and secreted TNF‐α, the different cellular localizations of TWE‐PRIL and APRIL suggest that they exert distinct biological roles.