TREX复合体在histone mRNA 的3'端加工和出核中的功能机制研究

在真核细胞中，绝大多数的mRNA均具有polyA尾，其出核转运依赖高度保守的TREX复合体。复制依赖型的histone mRNA（RD histone mRNA）是唯一一类不具有polyA 尾的mRNA，其3’端由茎环结构代替，它编码的组蛋白在细胞增殖等重要生物学过程中发挥关键作用。RD histone mRNA的3'端加工和出核过程受到严格的调控，然而，其中的分子机制还不十分清楚。我们前期研究发现：TREX组分ALYREF广泛而特异地结合在RD histone mRNA的茎环区域。在本项目中，我们将研究此特异性结合的分子机制；探索TREX在RD histone mRNA 加工和出核过程中的功能和机制；探究RD histone mRNA 的3’端加工和出核间的偶联。此研究将揭示调控RD histone mRNA表达的新机制，并为理解TREX的生理病理功能提供重要线索。

The highly conserved TREX complex (TREX) plays an important role in nuclear export of mRNAs containing polyA tail. Metazoan replication-dependent histone mRNAs (RD histone mRNAs) are the only eukaryotic mRNAs that lack a polyA tail, instead ending with a conserved stem loop structure. RD histone mRNAs encode histone proteins for packaging newly synthesized DNA in chromatin and plays key roles in many important biological processes, such as cell proliferation. The 3’ processing and nuclear export of RD histone mRNAs are tightly controlled, however, the underlying mechanism remains elusive. Our preliminary data demonstrate that ALYREF, a component of the TREX, specifically binds to a region upstream adjacent to stem loop on most RD histone mRNAs. Here, we plan to study how TREX is recruited to this specific region, investigate the function and mechanism of TREX in 3’ processing and nuclear export of RD histone mRNAs , reveal the mechanism for linking histone pre-mRNA processing to mRNA export. This study will reveal novel regulatory mechanisms for the expression of RD histone mRNA and provide important clues for understanding the physiological and pathological functions of TREX.