RBFOX2 regulated EYA3 isoforms partner with SIX4 or ZBTB1 to control transcription during myogenesis.
RBFOX2 regulated EYA3 isoforms partner with SIX4 or ZBTB1 to control transcription during myogenesis.
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DOI：
10.1016/j.isci.2023.108258
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发表时间：
2023-11-17
期刊：
影响因子：
5.8
通讯作者：
Giudice, Jimena
中科院分区：
文献类型：
--
作者：
Wiedner, Hannah J.;Blue, R. Eric;Sadovsky, Matheus;Mills, C. Allie;Wehrens, Xander H. T.;Herring, Laura E.;Giudice, Jimena
选择性剪接是一种流行的基因调控机制，估计超过95%的人类多外显子基因是选择性剪接的。在这里，我们描述了一种组织特异性的、发育调节的、高度保守的、与疾病相关的Eya3基因外显子7的选择性剪接事件。我们发现EYA3的表达对成肌细胞的增殖和分化至关重要。全基因组转录分析和基于质谱学的蛋白质组学研究发现，6个同源盒4(SIX4)和锌指及BTB结构域包含1(ZBTB1)是与EYA3相互作用决定基因表达的主要转录因子。EYA3亚型差异调节转录，表明剪接有助于肌肉细胞分化过程中基因表达的时间控制。最后，我们确定RNA结合的Fox-1同源物2(RBFOX2)是EYA3剪接的主要调控因子。总之，我们的发现说明了肌肉发生过程中选择性剪接和转录之间的相互作用。EYA3的表达对成肌细胞的增殖和分化至关重要EYA3与转录因子SIX4或ZBTB1相互作用决定基因表达EYA3亚型在肌肉发生过程中差异调节转录RBFOX2是调节EYA3剪接生理、分子生物学、OMICS的主要RNA结合蛋白
Alternative splicing is a prevalent gene-regulatory mechanism, with over 95% of multi-exon human genes estimated to be alternatively spliced. Here, we describe a tissue-specific, developmentally regulated, highly conserved, and disease-associated alternative splicing event in exon 7 of the eyes absent homolog 3 (Eya3) gene. We discovered that EYA3 expression is vital to the proliferation and differentiation of myoblasts. Genome-wide transcriptomic analysis and mass spectrometry-based proteomic studies identified SIX homeobox 4 (SIX4) and zinc finger and BTB-domain containing 1 (ZBTB1), as major transcription factors that interact with EYA3 to dictate gene expression. EYA3 isoforms differentially regulate transcription, indicating that splicing aids in temporal control of gene expression during muscle cell differentiation. Finally, we identified RNA-binding fox-1 homolog 2 (RBFOX2) as the main regulator of EYA3 splicing. Together, our findings illustrate the interplay between alternative splicing and transcription during myogenesis. EYA3 expression is critical for myoblast proliferation and differentiation EYA3 interacts with transcription factors SIX4 or ZBTB1 to dictate gene expression EYA3 isoforms differentially regulate transcription during myogenesis RBFOX2 is the main RNA-binding protein regulating EYA3 splicing Physiology; Molecular biology; Omics
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影响因子：
16.6
作者：
Freyermuth F;Rau F;Kokunai Y;Linke T;Sellier C;Nakamori M;Kino Y;Arandel L;Jollet A;Thibault C;Philipps M;Vicaire S;Jost B;Udd B;Day JW;Duboc D;Wahbi K;Matsumura T;Fujimura H;Mochizuki H;Deryckere F;Kimura T;Nukina N;Ishiura S;Lacroix V;Campan-Fournier A;Navratil V;Chautard E;Auboeuf D;Horie M;Imoto K;Lee KY;Swanson MS;de Munain AL;Inada S;Itoh H;Nakazawa K;Ashihara T;Wang E;Zimmer T;Furling D;Takahashi MP;Charlet-Berguerand N
通讯作者：
Charlet-Berguerand N
DOI：
10.1261/rna.078993.121
发表时间：
2022-04
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Hinkle ER;Wiedner HJ;Torres EV;Jackson M;Black AJ;Blue RE;Harris SE;Guzman BB;Gentile GM;Lee EY;Tsai YH;Parker J;Dominguez D;Giudice J
通讯作者：
Giudice J
影响因子：
5.3
作者：
Ikeda, K;Watanabe, Y;Kawakami, K
通讯作者：
Kawakami, K
影响因子：
8
作者：
Baudry, D;Faussillon, M;Jeanpierre, C
通讯作者：
Jeanpierre, C
影响因子：
4.6
作者：
Dolfini, Diletta;Andrioletti, Valentina;Mantovani, Roberto
通讯作者：
Mantovani, Roberto