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Human spliceosomal snRNA sequence variants generate variant spliceosomes
RNA ( IF 4.2 ) Pub Date : 2021-10-01 , DOI: 10.1261/rna.078768.121
Justin W Mabin 1 , Peter W Lewis 1 , David A Brow 1 , Heidi Dvinge 1
Affiliation  

Human pre-mRNA splicing is primarily catalyzed by the major spliceosome, comprising five small nuclear ribonucleoprotein complexes, U1, U2, U4, U5, and U6 snRNPs, each of which contains the corresponding U-rich snRNA. These snRNAs are encoded by large gene families exhibiting significant sequence variation, but it remains unknown if most human snRNA genes are untranscribed pseudogenes or produce variant snRNAs with the potential to differentially influence splicing. Since gene duplication and variation are powerful mechanisms of evolutionary adaptation, we sought to address this knowledge gap by systematically profiling human U1, U2, U4, and U5 snRNA variant gene transcripts. We identified 55 transcripts that are detectably expressed in human cells, 38 of which incorporate into snRNPs and spliceosomes in 293T cells. All U1 snRNA variants are more than 1000-fold less abundant in spliceosomes than the canonical U1, whereas at least 1% of spliceosomes contain a variant of U2 or U4. In contrast, eight U5 snRNA sequence variants occupy spliceosomes at levels of 1% to 46%. Furthermore, snRNA variants display distinct expression patterns across five human cell lines and adult and fetal tissues. Different RNA degradation rates contribute to the diverse steady state levels of snRNA variants. Our findings suggest that variant spliceosomes containing noncanonical snRNAs may contribute to different tissue- and cell-type–specific alternative splicing patterns.

中文翻译:


人类剪接体 snRNA 序列变异产生变异剪接体



人类前 mRNA 剪接主要由主要剪接体催化,剪接体由五个小核糖核蛋白复合物 U1、U2、U4、U5 和 U6 snRNP 组成,每个剪接体都含有相应的富含 U 的 snRNA。这些 snRNA 由表现出显着序列变异的大基因家族编码,但目前尚不清楚大多数人类 snRNA 基因是否是未转录的假基因或产生可能对剪接产生差异影响的变异 snRNA。由于基因复制和变异是进化适应的强大机制,我们试图通过系统分析人类 U1、U2、U4 和 U5 snRNA 变异基因转录本来解决这一知识差距。我们鉴定了 55 个在​​人类细胞中可检测表达的转录本,其中 38 个转录本并入 293T 细胞中的 snRNP 和剪接体中。所有 U1 snRNA 变体在剪接体中的丰度比标准 U1 低 1000 倍以上,而至少 1% 的剪接体含有 U2 或 U4 的变体。相比之下,8 个 U5 snRNA 序列变体以 1% 至 46% 的水平占据剪接体。此外,snRNA 变体在五种人类细胞系以及成人和胎儿组织中表现出不同的表达模式。不同的 RNA 降解率导致 snRNA 变体的稳态水平不同。我们的研究结果表明,含有非经典 snRNA 的变异剪接体可能有助于不同组织和细胞类型特异性的选择性剪接模式。
更新日期:2021-09-16
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