Regulation of mRNA stability through UPF1 and STAU1

Abstract

Posttranscriptional regulation processes regulate gene expression at the RNA level, including 5’ end capping, 3’ end processing, splicing, mRNA export, translation and mRNA stability. Of these, mRNA stability can be controlled by mRNA decay pathways and miRNA-mediated gene silencing. The mRNA decay pathway is the process of removing mRNA with abnormal or specific structure, through which the gene expression in the cell is regulated. Typical mRNA decay pathways include nonsense-mediated mRNA decay (NMD) and Staufen-mediated mRNA decay (SMD). The key factors of these mRNA decay pathways are up-frameshift factor 1 (UPF1) and Staufen (STAU), respectively. miRNA-mediated gene silencing is a mechanism by which gene expression is repressed by miRNA, a short noncoding RNA molecule consisting of approximately 22 nucleotides. miRNAs generally bind to the 3’UTR of their target mRNAs, which results in mRNA destabilization or translation inhibition. miRNAs are endogenously expressed in almost all eukaryotes and control RNA stability through a multi-step process. To date, researches on mRNA stability by NMD, SMD and miRNA regulation have been actively studied, but the specific targets and the resulting physiological effects need to be further investigated. In addition, the alternative pathway of NMD and miRNA is still unclear. In this thesis, I identify a new SMD target and reveal the relationship between NMD and increased translation. I also discuss the effects of reduced levels of STAU1 on neural differentiation and miRNA-mediated gene silencing controlled by UPF1.