Constant splice-isoform ratios in human lymphoblastoid cells support the concept of a splico-stat.

Authors:
Marcel Kramer, Klaus Huse, Uwe Menzel, Oliver Backhaus, Philip Rosenstiel, Stefan Schreiber, Jochen Hampe, Matthias Platzer
Year of publication:
2011
Volume:
187
Issue:
3
Issn:
0016-6731
Journal title abbreviated:
GENETICS
Journal title long:
Genetics
Impact factor:
4.644
Abstract: 
Splicing generates mature transcripts from genes in pieces in eukaryotic cells. Overwhelming evidence has accumulated that alternative routes in splicing are possible for most human and mammalian genes, thereby allowing formation of different transcripts from one gene. No function has been assigned to the majority of identified alternative splice forms, and it has been assumed that they compose inert or tolerated waste from aberrant or noisy splicing. Here we demonstrate that five human transcription units (WT1, NOD2, GNAS, RABL2A, RABL2B) have constant splice-isoform ratios in genetically diverse lymphoblastoid cell lines independent of the type of alternative splicing (exon skipping, alternative donor/acceptor, tandem splice sites) and gene expression level. Even splice events that create premature stop codons and potentially trigger nonsense-mediated mRNA decay are found at constant fractions. The analyzed alternative splicing events were qualitatively but not quantitatively conserved in corresponding chimpanzee cell lines. Additionally, subtle splicing at tandem acceptor splice sites (GNAS, RABL2A/B) was highly constrained and strongly depends on the upstream donor sequence content. These results also demonstrate that unusual and unproductive splice variants are produced in a regulated manner.