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.

Highlights

  • Alternative splicing (AS) is a major mechanism for modulating gene expression of an organism, allowing the synthesis of several structurally and functionally distinct Messenger RNA (mRNA) and protein isoforms from a unique gene

  • Lymphocyte antigen-6 (LY-6) superfamily members are cysteine-rich, generally GPI-anchored, cell surface proteins, which have definite or putative immune-related roles [15]. Among these LY-6 Major Histocompatibility Complex (MHC) class III region genes, Ly6g5b showed a particular behaviour in the regulation of its expression [13,16], involving an intron retention event in human and mouse, the rarest form of alternative splicing found in metazoan species [17]

  • We could detect the presence of the canonical Csnk2b transcript in each tested species and tissues (Figure 2), and it was the isoform expressed at the highest level

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Summary

Introduction

Alternative 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. LY-6 superfamily members are cysteine-rich, generally GPI-anchored, cell surface proteins, which have definite or putative immune-related roles [15] Among these LY-6 MHC class III region genes, Ly6g5b showed a particular behaviour in the regulation of its expression [13,16], involving an intron retention event in human and mouse, the rarest form of alternative splicing found in metazoan species [17]. It has been showed that these chimeras significantly exploit signal peptides and transmembrane domains, which could alter the cellular localisation of cognate proteins, and that chimeric RNAs are more tissue specific than non-chimeric transcripts [26] This novel mechanism directly related to AS could have an important role in evolution divergence. We have made a comparative analysis of human CSNK2B, LY6G5B, and CSNK2B-LY6G5B protein expressions

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