Panda, S. and Setia, M. and Kaur, N. and Shepal, V. and Arora, V. and Singh, D.K. and Mondal, A. and Teli, A. and Tathode, M. and Gajula, R. and Padhy, L.C. and Shiras, A. (2018) Noncoding RNA Ginir functions as anoncogene by associating with centrosomal proteins. PLoS Biol., 16 (10).

Text 42.Dr. Shiras A. (PLOS BIOLO.) open access.pdf Restricted to Repository staff only Download (18Mb) | Request a copy

Abstract

Long noncoding RNAs constitute a major fraction of the eukaryotic transcriptome, and together with proteins, they intricately fine-tune various growth regulatory signals to control cellular homeostasis. Here, we describe the functional characterisation of a novel pair of long intergenic noncoding RNAs (lincRNAs) comprised of complementary, fully overlapping sense and antisense transcripts Genomic Instability Inducing RNA (Ginir) and antisense RNA of Ginir (Giniras), respectively, from mouse cells. This transcript pair is expressed in a spatiotemporal manner during embryonic development. The individual levels of the sense and antisense transcripts are finely balanced during embryonic growth and in adult tissues. Functional studies of the individual transcripts performed using overexpression and knock-down strategies in mouse cells has led to the discovery that Ginir RNA is a regulator of cellular proliferation and can act as an oncogene having a preeminent role in malignant transformation. Mechanistically, we demonstrate that the oncogenic function of Ginir is mediated by its interaction with centrosomal protein 112 (Cep112). Additionally, we establish here a specific interaction between Cep112 with breast cancer type 1 susceptibility protein (Brca1), another centrosome-associated protein. Next, we prove that the mutual interaction between Cep112 with Brca1 is significant for mitotic regulation and maintenance of genomic stability. Furthermore, we demonstrate that the Cep112 protein interaction with Brca1 protein is impaired when an elevated level of Ginir RNA is present in the cells, resulting in severe deregulation and abnormality in mitosis, leading to malignant transformation. Inhibiting the Ginir RNA function in transformed cells attenuates transformation and restores genomic stability. Together, these findings unravel, to our knowledge, a hitherto-unknown mechanism of oncogenesis mediated by a long noncoding RNA and establishes a unique role of Cep112–Brca1 interaction being modulated by Ginir RNA in maintaining mitotic fidelity.

Item Type:	Article
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	13 Feb 2020 06:49
Last Modified:	09 Dec 2021 11:36
URI:	http://nccs.sciencecentral.in/id/eprint/632

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