The Role And Mechanism Of Long Non-coding RNA Gadd7 In The Control Of Cell Cycle And Apoptosis

Long noncoding RNAs (lncRNAs) are generally considered as non-protein coding transcripts longer than 200 nucleotides, which are the major proportion of the mammalian transcriptome. lncRNAs act functionally as RNAs, and can regulate the expression of genes through a diversity of mechanisms. Recently, a handful of studies have implicated long ncRNAs in a variety of disease states, especially in neurodegenerative diseases and cancer. However, the biological functions for lncRNAs have been poorly described, and remain to be further defined.gadd7 is one kind of lncRNAs which was isolated from Chinese hamster ovary (CHO) cells on the basis of increased level of RNA following treatment with UV radiation, and was found only expressed in hamster cells. The transcript for gadd7 was increased following several different types of DNA damage and other genotoxic stresses that elicit growth arrest. Overexpression of gadd7 led to a decrease in cell growth, but the understandings on precise molecular mechanisms of gadd7 in its cellular function are greatly limited in the present time.In this thesis, we further demonstrate that gadd7 is only expressed in hamster cells, and can been induced by both of growth arrest and DNA damage. Moreover, we have found that gadd7 is involved in the process of cell cycle control and apoptosis. Disruption of gadd7 in CHO-K1 cells significantly increases cyclin-dependent kinase 6 (Cdk6) protein and transcript levels. The control of Cdk6 expression mediated by gadd7 may involve the interaction of gadd7 with several proteins of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, which have well-defined splicing inhibitory activity, particularly hnRNP A2/B1 and TDP-43. Furthermore, gadd7 silencing also is followed by changes in the expression levels of several factors that control G1 phase, such as Cyclin D1, Cyclin A and Cdk4, indicating that different pathways regulated by gadd7 may be involved in the control of G1/S transition.Taken together, this study has demonstrated that gadd7 is involved in the control of cell cycle progression and apoptosis, and explored its molecular mechanisms, which provides novel insights into understanding on lncRNAs.