Abstract
BackgroundRegulation of the expression of particular genes can rely on mechanisms that are different from classical transcriptional and translational control. The LY6G5B and LY6G6D genes encode LY-6 domain proteins, whose expression seems to be regulated in an original fashion, consisting of an intron retention event which generates, through an early premature stop codon, a non-coding transcript, preventing expression in most cell lines and tissues.ResultsThe MHC LY-6 non-coding transcripts have shown to be stable and very abundant in the cell, and not subject to Nonsense Mediated Decay (NMD). This retention event appears not to be solely dependent on intron features, because in the case of LY6G5B, when the intron is inserted in the artificial context of a luciferase expression plasmid, it is fully spliced but strongly stabilises the resulting luciferase transcript. In addition, by quantitative PCR we found that the retained and spliced forms are differentially expressed in tissues indicating an active regulation of the non-coding transcript. EST database analysis revealed that these genes have an alternative expression pathway with the formation of Transcription Induced Chimeras (TIC). This data was confirmed by RT-PCR, revealing the presence of different transcripts that would encode the chimeric proteins CSNKβ-LY6G5B and G6F-LY6G6D, in which the LY-6 domain would join to a kinase domain and an Ig-like domain, respectively.ConclusionIn conclusion, the LY6G5B and LY6G6D intron-retained transcripts are not subjected to NMD and are more abundant than the properly spliced forms. In addition, these genes form chimeric transcripts with their neighbouring same orientation 5' genes. Of interest is the fact that the 5' genes (CSNKβ or G6F) undergo differential splicing only in the context of the chimera (CSNKβ-LY6G5B or G6F-LY6G6C) and not on their own.
Highlights
Regulation of the expression of particular genes can rely on mechanisms that are different from classical transcriptional and translational control
LY6G5B and LY6G6D transcript expression The LY6G6D and LY6G5B genes express a small first intron (98 and 148 nucleotides, respectively) in the open reading frame which tends to be retained in the majority of cell lines and tissues, both in human and mouse RNAs [12]
To better understand the regulation of expression of these genes we performed a detailed analysis of the two transcripts of the LY6G5B gene and their relative levels in some cell lines and tissues by real time Reverse Transcription-PCR (RT-PCR)
Summary
Regulation of the expression of particular genes can rely on mechanisms that are different from classical transcriptional and translational control. The human Major Histocompatibility Complex (MHC) is located at chromosome 6p21.3, and is ~4 Mb in length It consists of three regions, the class I and class II regions flanking the central class III region. The study of the class III region genes, especially the novel genes with a potential role in the immune system, may provide insights into the understanding of these diseases. Transcriptome studies of some MHC class III region genes indicate a high rate of different splicing events. Strong associations have been found between Rheumatoid Arthritis and the segment of the MHC class III region which includes these LY6 members. The characterisation of these transcripts is of great relevance for the understanding of human diseases
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