Investigation of RAG1 in lymphoid and brain cells: Understanding mechanism and regulation

Abstract

In summary, we show that RAG1 expression is regulated through a novel miRNA (miR- 29c) mediated mechanism and establish that as an additional mode of RAG1 regulation. Studies described in the thesis reveal that among the 3 clinically approved HIV integrase inhibitors (Elvitegravir, Dolutegravir, and Raltegravir) investigated, Elvitegravir can cause harmful effects on long term treatment. In nonlymphoid organ, brain, we observe that RAG1, but not RAG2 is expressed in an age dependent manner. Importantly, RAG1 expression was primarily limited to astrocytes and its expression in neuron appears to be minimal. Further, various lines of evidence indicate that RAG1 expression in the astrocytes may play a critical role in cell proliferation. Besides, absence of RAG1 expression may lead to elevated levels of DNA breaks culminating in cellular senescence as seen in RAG1 knockout mice. Thus, RAG1 could play a potential role in the maintenance of cell homeostasis in mouse brain