Intron retention and transcript chimerism conserved across mammals: Ly6g5b and Csnk2b-Ly6g5b as examples

Abstract

BackgroundAlternative splicing (AS) is a major mechanism for modulating gene expression of an organism, allowing the synthesis of several structurally and functionally distinct mRNAs and protein isoforms from a unique gene. Related to AS is the Transcription Induced Chimerism (TIC) or Tandem Chimerism, by which chimeric RNAs between adjacent genes can be found, increasing combinatorial complexity of the proteome. The Ly6g5b gene presents particular behaviours in its expression, involving an intron retention event and being capable to form RNA chimera transcripts with the upstream gene Csnk2b. We wanted to characterise these events more deeply in four tissues in six different mammals and analyse their protein products.ResultsWhile canonical Csnk2b isoform was widely expressed, Ly6g5b canonical isoform was less ubiquitous, although the Ly6g5b first intron retained transcript was present in all the tissues and species analysed. Csnk2b-Ly6g5b chimeras were present in all the samples analysed, but with restricted expression patterns. Some of these chimeric transcripts maintained correct structural domains from Csnk2b and Ly6g5b. Moreover, we found Csnk2b, Ly6g5b, and Csnk2b-Ly6g5b transcripts that present exon skipping, alternative 5' and 3' splice site and intron retention events. These would generate truncated or aberrant proteins whose role remains unknown. Some chimeric transcripts would encode CSNK2B proteins with an altered C-terminus, which could affect its biological function broadening its substrate specificity. Over-expression of human CSNK2B, LY6G5B, and CSNK2B-LY6G5B proteins, show different patterns of post-translational modifications and cell distribution.ConclusionsLy6g5b intron retention and Csnk2b-Ly6g5b transcript chimerism are broadly distributed in tissues of different mammals.

CSNK2B splice site mutations in patients cause intellectual disability with or without myoclonic epilepsy

“…Moreover, we observed an aberrant transcript with an intron‐5 read through predominantly produced from the wild‐type allele. However, this aberrant transcript was previously described as a minor transcript (Hernández‐Torres et al., ). Sequencing analysis of the aberrant mRNA form in patient 2 showed the abnormal absence of exon 3 in the CSNK2B mRNA with respect of controls that were normal (Fig.…”

Intergenically Spliced Chimeric RNAs in Cancer

“…It is essentially an alternative splicing between exons of neighboring genes [26] (Figure 2D). Although only a handful examples of cis-spliced RNA chimeras were experimentally confirmed in mammalian cells [27], in-silico analysis and paired-end RNA-sequencing have successfully identified many chimeric RNAs composed of two neighboring genes, which could originate from transcriptional read-through [27-33]. In fact, it is postulated that 4%-5% of tandem gene pairs in the human genome can participate in this process and form chimeric RNAs [28, 34].…”

ChimPipe: accurate detection of fusion genes and transcription-induced chimeras from RNA-seq data

“…Initially thought to be an exception, this mechanism was found to be widespread in mammals when large collections of ESTs (Expressed Sequence Tags) and cDNAs (complementary DNA) became available and were mapped to the genome [3–5], and when the ENCODE (ENCyclopedia Of DNA Elements) consortium systematically surveyed the transcriptome associated to annotated protein coding genes [6–9]. Read-throughs occur between annotated exons of adjacent genes, preferentially between the penultimate exon of the upstream (5’) gene and the second exon of the downstream (3’) gene [3], resulting in new proteins containing domains from the two parent genes, therefore increasing the diversity of a species proteome [1, 3, 4, 10, 11]. They are also largely conserved across vertebrates [11, 12], and could be a way to regulate the expression of one or both parent genes [12].…”

“…Read-throughs occur between annotated exons of adjacent genes, preferentially between the penultimate exon of the upstream (5’) gene and the second exon of the downstream (3’) gene [3], resulting in new proteins containing domains from the two parent genes, therefore increasing the diversity of a species proteome [1, 3, 4, 10, 11]. They are also largely conserved across vertebrates [11, 12], and could be a way to regulate the expression of one or both parent genes [12]. …”