Tissue-specific SEC31A alternative splicing is regulated by RBM47 and controls lipid transport.

IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA Pub Date : 2025-05-28 DOI:10.1261/rna.080572.125
Felix Ostwaldt, Sarah Ploessner, Benjamin Dimos-Roehl, Marco Preussner, Florian Heyd
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引用次数: 0

Abstract

The importance of coat protein complex II (COPII) for protein secretion has been known for decades. However, how large cargo like pro-collagens or chylomicrons are secreted remains incompletely understood, as COPII vesicles are usually too small to accommodate such bulky cargo. Here we introduce alternative splicing as another regulatory layer in controlling secretion of large cargo. We use RNA-Seq data from various human tissues to identify tissues-specific alternative splicing in secretion-associated genes. This identifies an uncharacterized exon in SEC31A, a component of the COPII machinery, whose inclusion is highly tissue-specific, with high inclusion for example in digestive tissues. We show that inclusion of this exon increases lipid transport, thereby connecting SEC31A alternative splicing with the secretion of large cargo. Furthermore, by correlating SEC31A alternative splicing with the expression of RNA-binding proteins across multiple tissues, we identify and then validate RBM47 as the regulator of SEC31A alternative splicing. This serves as proof-of-principle for a broadly applicable in silico approach to facilitate the identification of trans-acting factors controlling tissue-specific alternative splicing.

组织特异性SEC31A选择性剪接受RBM47调控并控制脂质转运。
几十年来,人们已经知道外壳蛋白复合物II (COPII)对蛋白质分泌的重要性。然而,像前胶原或乳糜微粒这样的大货物是如何分泌的仍不完全清楚,因为COPII囊泡通常太小,无法容纳如此庞大的货物。在这里,我们引入选择性剪接作为控制大货分泌的另一个调节层。我们使用来自各种人体组织的RNA-Seq数据来鉴定分泌相关基因的组织特异性选择性剪接。这在SEC31A中发现了一个未表征的外显子,SEC31A是COPII机制的一个组成部分,其包含具有高度的组织特异性,例如在消化组织中具有高包含性。我们发现这个外显子的包含增加了脂质转运,从而将SEC31A选择性剪接与大货物的分泌联系起来。此外,通过将SEC31A选择性剪接与多个组织中rna结合蛋白的表达相关联,我们确定并验证了RBM47是SEC31A选择性剪接的调节因子。这可以作为广泛适用的硅方法的原理证明,以促进识别控制组织特异性选择性剪接的交易作用因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
RNA
RNA 生物-生化与分子生物学
CiteScore
8.30
自引率
2.20%
发文量
101
审稿时长
2.6 months
期刊介绍: RNA is a monthly journal which provides rapid publication of significant original research in all areas of RNA structure and function in eukaryotic, prokaryotic, and viral systems. It covers a broad range of subjects in RNA research, including: structural analysis by biochemical or biophysical means; mRNA structure, function and biogenesis; alternative processing: cis-acting elements and trans-acting factors; ribosome structure and function; translational control; RNA catalysis; tRNA structure, function, biogenesis and identity; RNA editing; rRNA structure, function and biogenesis; RNA transport and localization; regulatory RNAs; large and small RNP structure, function and biogenesis; viral RNA metabolism; RNA stability and turnover; in vitro evolution; and RNA chemistry.
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