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通过保留的CELF蛋白UNC-75在Caenorhabditis elegans中抑制替代拼接的神经元特异性抑制

Pallavi Pilaka-Akella¹, Nour H Sadek¹, Daniel Fusca²

¹Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, Ontario, Canada M5S 3G5.

|March 10, 2025

概括

组织特定的替代拼接依赖于RNA结合蛋白 (RBPs) 和cis元素. 研究人员确定了保留的UNC-75结合基因,该基因调节了C. elegans的神经外子,证明了它们在强大的拼接结果中的作用.

科学领域:

分子生物学分子生物学
遗传学遗传学是一个
发展生物学发展生物学

背景情况:

替代拼接对于从有限的基因组中生成多样化的蛋白质组至关重要.
RNA结合蛋白 (RBPs) 和 cis调节元件协调组织特异性的替代拼接.
CUG结合蛋白和类似ETR的RBPs家族 (CELF) 是关键的调节者,与神经和肌肉疾病有关.

研究的目的:

通过在Caenorhabditis elegans中通过神经元丰富的CELF正位数UNC-75研究组织特异性拼接调节的体内机制.
描述保存的cis元素的作用及其与UNC-75的相互作用,以控制替代的外子拼接.

主要方法:

序列对齐以识别保存的UNC-75绑定模式.
在C. elegans中进行基因操纵,包括基因淘汰 (UNC-75的损失) 和cis元素的局部定向突变发生.
在体内拼接测试以评估神经元和肌肉细胞中的外子使用情况.
异质拼接试验,以测试UNC-75图案在不同环境中的功能.

主要成果:

鉴定了保存的UNC-75结合基因,覆盖了动物园-1基因中神经抑制的替代前体的5'拼接部位和3'拼接部位的上游.
丢失UNC-75或破坏这些cis元素导致神经元中替代性外的显著抑制.
肌肉中UNC-75的错误表达诱导了替代性前体的强烈跳过,模仿神经元拼接.
引入异质拼接部位的UNC-75基因增加了相邻的替代外显子的跳过.

结论:

通过UNC-75结合的cis元素的特定排列和组合可以在体内带来强大的,组织特定的拼接结果.
这项研究阐明了由CELF家族蛋白及其相关的cis元素调节神经元拼接的一个关键机制.
这些发现凸显了RBPs和cis元素在发育过程中微调基因表达中的保留重要性.

关键词:

这里是C. elegans.它们是CELF蛋白质.在RNA结合蛋白质中的RNA结合蛋白.处理RNA处理RNA的过程 UNC-75 UNC-75 UNC-75 是一个这是WormBase的基础.另一个替代拼接方法是拼接.基因表达的基因表达方式

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