Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid, Madrid, Spain.
BMC Genomics. 2013 Mar 22;14:199. doi: 10.1186/1471-2164-14-199.
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. 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.
While 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.
Ly6g5b intron retention and Csnk2b-Ly6g5b transcript chimerism are broadly distributed in tissues of different mammals.
可变剪接（AS）是调节生物体基因表达的主要机制，允许从一个独特的基因合成几种结构和功能不同的 mRNA 和蛋白质同工型。与 AS 相关的是转录诱导嵌合体（TIC）或串联嵌合体，通过这种嵌合体可以在相邻基因之间找到嵌合 RNA，从而增加蛋白质组的组合复杂性。Ly6g5b 基因在其表达中表现出特殊的行为，涉及内含子保留事件，并能够与上游基因 Csnk2b 形成 RNA 嵌合体转录本。我们希望在六种不同哺乳动物的四种组织中更深入地研究这些事件，并分析它们的蛋白质产物。
虽然经典的 Csnk2b 同工型广泛表达，但 Ly6g5b 经典同工型并不普遍存在，尽管 Ly6g5b 第一个内含子保留的转录本存在于所有分析的组织和物种中。Csnk2b-Ly6g5b 嵌合体存在于所有分析的样本中，但表达模式有限。这些嵌合转录本中的一些保留了 Csnk2b 和 Ly6g5b 的正确结构域。此外，我们发现 Csnk2b、Ly6g5b 和 Csnk2b-Ly6g5b 转录本存在外显子跳跃、5' 和 3' 剪接位点和内含子保留事件。这将产生截断或异常的蛋白质，其作用仍然未知。一些嵌合转录本将编码具有改变的 C 末端的 CSNK2B 蛋白，这可能会影响其生物学功能，扩大其底物特异性。人 CSNK2B、LY6G5B 和 CSNK2B-LY6G5B 蛋白的过表达显示出不同的翻译后修饰和细胞分布模式。
Ly6g5b 内含子保留和 Csnk2b-Ly6g5b 转录本嵌合体在不同哺乳动物的组织中广泛分布。
