The Exon Junction Complex Protein Y14 : a Substrate and a Partner of Arginine Methyltransferases

Autor: Tzu-Wei Chuang, 莊子瑋
Rok vydání: 2006
Druh dokumentu: 學位論文 ; thesis
Popis: 94
In eukaryotic cells, precursor mRNAs undergo several steps of nuclear processing, including 5’-capping, splicing, and polyadenylation, to form mature mRNAs. Upon splicing, the exon junction complex (EJC) is deposited on the spliced mRNA and participates in post-splicing events, such as mRNA export, nonsense-mediated mRNA decay (NMD), and translation control. The EJC is composed of several proteins, in which a stable heterodimer of Y14 and Mago is the core component. The EJC functions in nuclear export of spliced mRNA by recruiting the mRNA export factor TAP, in part via the interaction of Y14/Mago with TAP. Moreover, Y14/Mago directly promotes NMD and translation by its association with several key factors involved in these events. Many RNA-binding proteins undergo post-translational modifications such as phosphorylation and methylation. We previously demonstrated that Y14 is phosphorylated at the duplicated RS dipeptides and that such a phosphorylation abolishes Y14 interaction with several EJC and its associated factors (Hsu et al. JBC 280, 34507-34512; 2005). In this thesis, we found that non-phosphorylated Y14 interacted with arginine methyltransferase PRMT5 and its methylosome partner pICln. The interaction of Y14 with the methylosome required intact structure of Y14, but not its heterodimerization with Mago, and such an interaction could be disrupted by Y14 phosphorylation. Moreover, we functionally analyzed the effect of Y14 overexpression on the methylosome. Our preliminary data suggested that Y14 may regulate the complex formation of the methylosome, and perhaps further influence its enzyme activity. Our study also unveiled methylation of Y14 at multiple arginine residues in the C-terminal region in vitro by PRMT1. Methylation of Y14 can be blocked by RS dipeptide phosphorylation. Althonth Y14 is indeed methylated in vivo, which methyltransferase is responsible for Y14 methylation is presently unknown. The differential modification of the C-terminal domain of Y14 may modulate the conformation of Y14-containing mRNPs and perhaps the functions of Y14.
Databáze: Networked Digital Library of Theses & Dissertations
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