Function on Non-Coding RNA, MALAT1, in B-cell development and Lymphoma

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ABSTRACT Human B-cell lymphoma is a significant clinical problem that is rising in incidence and prevalence as the American population ages. At the molecular level, changes in gene expression are central to both oncogenesis and developmental processes. Recently it has come to light that non-coding RNAs are central players in regulating gene expression. Extending our prior work in microRNAs, we now propose to analyze the contribution of a long non-coding RNA, Malat-1 to B-cell development and oncogenesis. Our preliminary data shows that Malat-1 is differentially regulated during the activation of B-cells, and recent publications implicate it as a target of activation-induced deaminase (AID), which can induce oncogenic translocations in germinal center B-cells. We therefore hypothesize that Malat1 may influence B-cell development and oncogenesis. Here, we propose to study the expression pattern of Malat1 in B-cell differentiation, and to understand its oncogenic function via gain and loss-of-function approaches in murine B-cells. These studies will delve into a novel, poorly understood field, as virtually nothing is known about long non-coding RNAs in B-cell lymphoma. In completing these aims, we will generate the necessary preliminary data to apply for a R01 grant. The completion of these goals promises to significantly increase our understanding of critical biological and pathological processes.