IMPC: The role of SARNP in hearing loss

IMPC：SARNP 在听力损失中的作用

• 批准号: MR/P026109/1
• 负责人: Stuart Wilson
• 金额: $ 3.85万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP026109%2F1
• 关键词: IMPC; role; SARNP; hearing; loss

DNA resides within the nucleus in human cells and encodes the information to make proteins. Messenger RNA (mRNA) is copied from DNA and is then transported to the cytoplasm where it is translated to make proteins. A key protein complex involved in the transport of mRNA from the nucleus to the cytoplasm is TREX. We previously identified SARNP protein as a subunit of the TREX mRNA export complex which forms an ATP dependent trimer with two other subunits, ALYREF and UAP56 and plays a role in mRNA export. Mutations in TREX subunits are associated with a number of human conditions including X-linked intellectual disability (THOC2) and Beaulieu-Boycott-Innes syndrome (THOC6). Although the preliminary phenotypic screening of a SARNP knockout heterozygote has identified a hearing defect, the molecular and functional mechanisms controlled by this protein in the auditory system are completely unknown. In this project we will combine our expertise in mRNA export mechanisms with that in hearing research to identify the cellular defects leading to hearing loss in these mice.

DNA存在于人类细胞的细胞核中，并对信息进行编码以制造蛋白质。信使RNA （mRNA）是从DNA中复制出来的，然后被运送到细胞质中，在那里被翻译成蛋白质。参与mRNA从细胞核转运到细胞质的关键蛋白复合体是TREX。我们之前发现SARNP蛋白是TREX mRNA输出复合体的一个亚基，该复合体与另外两个亚基ALYREF和UAP56形成ATP依赖性三聚体，并在mRNA输出中发挥作用。TREX亚基突变与许多人类疾病有关，包括x连锁智力残疾（THOC2）和beaulieu - boycot - innes综合征（THOC6）。虽然SARNP敲除杂合子的初步表型筛选已经确定了听力缺陷，但听觉系统中由该蛋白控制的分子和功能机制是完全未知的。在这个项目中，我们将结合我们在mRNA输出机制和听力研究方面的专业知识来确定导致这些小鼠听力损失的细胞缺陷。