A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of mRNA species by alternative polyadenylation, mRNA splicing and transcription initiation

Human TRAF-3 is a signaling molecule that interacts with the cytoplasmic ta ils of CD40 and other TNF-receptor family members. TRAF-3 mRNA is expressed as two major classes of approximately 2 and 8 kb and a number of TRAF-3 en coding cDNA clones differ in discrete gene segments. Because this variety o f mRNA species could result from mRNA processing events and/or multiple gen es, the structure and localization of TRAF-3 encoding gene elements were de termined. FISH and radiation hybrid mapping demonstrated that TRAF-3 is loc ated at chromosome 14q32.3, approximately 1 Mb centromeric to the Ig heavy chain gene complex. Physical mapping of four overlapping genomic PAC clones established that TRAF-3 transcripts are encoded by a single gene, comprise d of 13 exons and spanning 130 kb. Alternative polyadenylation in the mRNA segment encoded by exon 12 accounts for the difference between the 2 kb and the 8 kb classes of transcripts. Alternative mRNA splicing in the coding r egion (encoded by exons 3-12) generates transcripts which delete exons 8 (7 5 nt), 7 + 8 (156 nt) or 8 + 9 (168 nt) and that encode distinct protein is oforms (Delta 25, Delta 52 and Delta 56 aa, respectively). Alternative spli cing of exon 2 (139 nt) and alternative transcriptional initiation result i n mRNA species with distinct 5'UTRs. Together, these data indicate that a s ingle TRAF-3 gene encodes a variety of mRNA species by a combination of alt ernative polyadenylation, alternative mRNA splicing and/or alternative init iation. (C) 1999 Elsevier Science Ltd. All rights reserved.