Poster abstracts

Poster number 63 submitted by Lalith Gunawardane

Defining the “interactome” of a long non-coding RNA

Lalith Gunawardane (Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106), Saba Valadkhan (Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106)

Abstract:
The recent large scale genomic analyses have indicated that long non-coding RNAs constitute a major group of regulatory factors in higher eukaryotes. However, due to their novelty, very few studies have addressed their cellular function and their mechanistic strategies in sufficient detail. In our studies, we have focused on the BORG RNA, a ~2700 nucleotide long message which is induced in response to the activation of BMP2 signaling pathway. BORG is a spliced and polyadenylated RNA, however, it is localized to the nuclei. Tissue expression analyses have indicated that in the mouse, BORG has a very restricted expression pattern, with its expression being detectable only in neural tissues and kidneys. Analysis of the function of BORG in the N2A neuroblastoma cells, a commonly used neuronal differentiation model, indicated that BORG is required for differentiation in these cells. While shRNA-mediated knockdown of BORG blocked neuronal differentiation in N2A cells, BORG overexpression resulted in faster and more efficient morphological differentiation in these cells. In order to define the role of BORG in differentiation of other cell types, we determined the effect of its overexpression in the C2C12 myoblasts and C3H10T1/2 fibroblastic cells. Interestingly, BORG overexpression resulted in reprogramming of both these cell lines into neurons. In order to gain insight into the mechanism of this RNA-mediated reprogramming, we have launched a comprehensive study of the factors which interact with this non-coding RNA. Preliminary results from this study will be presented.

Keywords: long non-coding RNAs, BORG, reprogramming