由 GEMIN5 翻译水平改变所驱动的替代剪接事件。

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-08-28 DOI:10.1080/15476286.2024.2394755
Rosario Francisco-Velilla, Salvador Abellan, Juan Antonio Garcia-Martin, Juan Carlos Oliveros, Encarnacion Martinez-Salas
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引用次数: 0

摘要

GEMIN5 是一种多功能蛋白质,参与 RNA 生物学的各个方面,包括 snRNPs 的生物生成和翻译控制。GEMIN5 水平的降低会使选择性的一组 mRNA 发生不同的翻译,而降低蛋白质稳定性或诱导结构构象变化的双唇变体与神经系统疾病有关。在这里,我们发现 GEMIN5 的上调可能是有害的,因为它改变了 mRNA 的稳定状态,并增强了参与多种细胞过程的基因的替代剪接(AS)事件。对GEMIN5水平较高的细胞中与多聚体相关的mRNA进行RNA-Seq鉴定后发现,相当一部分差异AS事件是在翻译过程中发生的。mRNA与多聚体的关联取决于AS事件的类型,在外显子跳越的情况下更为常见。不过,出现开放阅读框破坏的基因比例并无重大差异。重要的是,多聚体中mRNA的不同AS事件最终导致蛋白质失去功能,编码控制细胞生长的因子。在 GEMIN5 上调时,参与多聚体中 AS 事件的 mRNA 种类繁多,这支持了一种观点,即这种多功能蛋白质是作为基因表达平衡器进化而来的,与其作为 SMN 复合物成员和蛋白质合成调节器的双重角色相一致,最终影响了细胞的平衡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Alternative splicing events driven by altered levels of GEMIN5 undergo translation.

GEMIN5 is a multifunctional protein involved in various aspects of RNA biology, including biogenesis of snRNPs and translation control. Reduced levels of GEMIN5 confer a differential translation to selective groups of mRNAs, and biallelic variants reducing protein stability or inducing structural conformational changes are associated with neurological disorders. Here, we show that upregulation of GEMIN5 can be detrimental as it modifies the steady state of mRNAs and enhances alternative splicing (AS) events of genes involved in a broad range of cellular processes. RNA-Seq identification of the mRNAs associated with polysomes in cells with high levels of GEMIN5 revealed that a significant fraction of the differential AS events undergo translation. The association of mRNAs with polysomes was dependent on the type of AS event, being more frequent in the case of exon skipping. However, there were no major differences in the percentage of genes showing open-reading frame disruption. Importantly, differential AS events in mRNAs engaged in polysomes, eventually rendering non-functional proteins, encode factors controlling cell growth. The broad range of mRNAs comprising AS events engaged in polysomes upon GEMIN5 upregulation supports the notion that this multifunctional protein has evolved as a gene expression balancer, consistent with its dual role as a member of the SMN complex and as a modulator of protein synthesis, ultimately impinging on cell homoeostasis.

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来源期刊
RNA Biology
RNA Biology 生物-生化与分子生物学
CiteScore
8.60
自引率
0.00%
发文量
82
审稿时长
1 months
期刊介绍: RNA has played a central role in all cellular processes since the beginning of life: decoding the genome, regulating gene expression, mediating molecular interactions, catalyzing chemical reactions. RNA Biology, as a leading journal in the field, provides a platform for presenting and discussing cutting-edge RNA research. RNA Biology brings together a multidisciplinary community of scientists working in the areas of: Transcription and splicing Post-transcriptional regulation of gene expression Non-coding RNAs RNA localization Translation and catalysis by RNA Structural biology Bioinformatics RNA in disease and therapy
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