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 tails 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 encoding cDNA clones differ in discrete gene segments. Because this variety of mRNA species could result from mRNA processing events and/or multiple genes, the structure and localization of TRAF-3 encoding gene elements were determined. FISH and radiation hybrid mapping demonstrated that TRAF-3 is located 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, comprised 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 region (encoded by exons 3-12) generates transcripts which delete exons 8 (75 nt), 7+8 (156 nt) or 8+9 (168 nt) and that encode distinct protein isoforms (delta25, delta52 and delta56 aa, respectively). Alternative splicing of exon 2 (139 nt) and alternative transcriptional initiation result in mRNA species with distinct 5'UTRs. Together, these data indicate that a single TRAF-3 gene encodes a variety of mRNA species by a combination of alternative polyadenylation, alternative mRNA splicing and/or alternative initiation.
van Eyndhoven
W G
WG
Laboratory of Molecular Immunology, Columbia University, New York, NY 10032, USA.
Frank
D
D
Kalachikov
S
S
Cleary
A M
AM
Hong
D I
DI
Cho
E
E
Nasr
S
S
Perez
A J
AJ
Mackus
W J
WJ
Cayanis
E
E
Wellington
S
S
Fischer
S G
SG
Warburton
D
D
Lederman
S
S
D017398:Alternative Splicing / Q000235:genetics*; D001482:Base Composition; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14 / Q000276:immunology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D005091:Exons; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D020161:Physical Chromosome Mapping; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D048008:TNF Receptor-Associated Factor 3; D014158:Transcription, Genetic / Q000235:genetics*; D020506:Untranslated Regions / Q000737:chemistry; D016335:Zinc Fingers / Q000235:genetics
D018076:DNA, Complementary; D005819:Genetic Markers; D011506:Proteins; D012333:RNA, Messenger; D048008:TNF Receptor-Associated Factor 3; D020506:Untranslated Regions