title: Huge splicing frequency in human Y chromosomal UTY gene.
abstract: Over 90% of human genes produce more than one mRNA by alternative splicing (AS). Human UTY (ubiquitously transcribed tetratricopeptide repeat protein on the chromosome Y) has six mRNA-transcripts. UTY is subject to interdisciplinary approaches such as Y chromosomal genetics or development of leukemia immunotherapy based on UTY-specific peptides. Investigating UTY expression in a normal and leukemic setting we discovered an exceptional splicing phenomenon fostering huge transcript diversity. Transcript sequencing identified 90 novel AS-events being almost randomly combined in 284 new transcripts. We uncovered a novel system of transcript architecture and genomic organization in UTY. On a basis of a new UTY-splicing multigraph including a mathematical model we calculated the theoretical yield to exceed 1.3 billion distinct transcripts. To our knowledge, this is the greatest estimated transcript diversity by AS. On protein level we demonstrated interaction of AS-derived proteins with new interactors by yeast-two-hybrid assay. For translational research we predicted new UTY-peptide candidates for leukemia therapy development. Our study provides new insights into the complexity of human alternative splicing and its potential contribution to the transcript diversity of the transcriptome.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Laaser
authors.forename: Fabian J
authors.initials: FJ
authors.lastname: Theis
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D015778:Minor Histocompatibility Antigens; D008962:Models, Theoretical; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques
chemical_list: D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C484453:UTY protein, human