IMPC: The role of SARNP in hearing loss

DNA存在于人类细胞的细胞核内，并编码信息以制造蛋白质。信使RNA（mRNA）从DNA复制，然后被运送到细胞质，在那里它被翻译成蛋白质。参与mRNA从细胞核转运到细胞质的关键蛋白质复合物是TREX。我们先前将SARNP蛋白鉴定为TREX mRNA输出复合物的亚基，其与另外两个亚基（TREREF和UAP 56）形成ATP依赖性三聚体，并在mRNA输出中起作用。TREX亚基中的突变与许多人类疾病相关，包括X连锁智力残疾（THOC 2）和Beaulieu-Boycott-Innes综合征（THOC 6）。虽然SARNP敲除杂合子的初步表型筛选已经确定了听力缺陷，但这种蛋白质在听觉系统中控制的分子和功能机制完全未知。在这个项目中，我们将联合收割机结合我们在mRNA输出机制和听力研究方面的专业知识，以确定导致这些小鼠听力损失的细胞缺陷。

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.