title: The human AKNA gene expresses multiple transcripts and protein isoforms as a result of alternative promoter usage, splicing, and polyadenylation.
abstract: We previously showed that the human AKNA gene encodes an AT-hook transcription factor that regulates the expression of costimulatory cell surface molecules on lymphocytes. However, AKNA cDNA probes hybridize with multiple transcripts, suggesting either the existence of other homologous genes or a complex regulation operating on a single gene. Here we report evidence for the latter, as we find that AKNA is encoded by a single gene that spans a 61-kb locus of 24 exons on the fragile FRA9E region of human chromosome 9q32. This gene gives rise to at least nine distinct transcripts, most of which are expressed in a tissue-specific manner in lymphoid organs. Many of the AKNA transcripts originate from alternative splicing; others appear to derive from differential polyadenylation and promoter usage. The alternative AKNA transcripts are predicted to encode overlapping protein isoforms, some of which (p70 and p100) are readily detectable using a polyclonal anti-AKNA antisera that we generated. We also find that AKNA PEST-dependent cleavage into p50 polypeptides is targeted to mature B cells and appears to be required for CD40 upregulation. The unusual capacity of the AKNA gene to generate multiple transcripts and proteins may reflect its functional diversity, and it may also provide a fail-safe mechanism that preserves AKNA expression.
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Sims-Mourtada
authors.forename: Shirley
authors.initials: S
authors.lastname: Bruce
authors.forename: Morgan R
authors.initials: MR
authors.lastname: McKeller
authors.forename: Roberto
authors.initials: R
authors.lastname: Rangel
authors.forename: Liliana
authors.initials: L
authors.lastname: Guzman-Rojas
authors.forename: Kelly
authors.initials: K
authors.lastname: Cain
authors.forename: Cristina
authors.initials: C
authors.lastname: Lopez
authors.forename: Drazen B
authors.initials: DB
authors.lastname: Zimonjic
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Popescu
authors.forename: John
authors.initials: J
authors.lastname: Gordon
authors.forename: Miles F
authors.initials: MF
authors.lastname: Wilkinson
authors.forename: Hector
authors.initials: H
authors.lastname: Martinez-Valdez
mesh_terms: D017398:Alternative Splicing; D001402:B-Lymphocytes / Q000378:metabolism; D015153:Blotting, Western; D019013:CD40 Antigens / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D005091:Exons; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008221:Lymphoid Tissue / Q000378:metabolism; D009687:Nuclear Proteins; D026723:Polyadenylation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C423232:AKNA protein, human; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors