Mechanism of Wnt signaling induced down regulation ofmrhllong non-coding RNA in mouse spermatogonial cells

Akhade, Vijay Suresh, Dighe, Shrinivas Nivrutti ORCID: https://orcid.org/0000-0002-2826-8733, Kataruka, Shubhangini and Rao, Manchanahalli R. Satyanarayana 2016. Mechanism of Wnt signaling induced down regulation ofmrhllong non-coding RNA in mouse spermatogonial cells. Nucleic Acids Research 44 (1) , pp. 387-401. 10.1093/nar/gkv1023

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Abstract

Long non coding RNAs (lncRNAs) have emerged as important regulators of various biological processes. LncRNAs also behave as response elements or targets of signaling pathway(s) mediating cellular function. Wnt signaling is important in regulating mammalian spermatogenesis. Mrhl RNA negatively regulates canonical Wnt pathway and gets down regulated upon Wnt signaling activation in mouse spermatogonial cells. Also, mrhl RNA regulates expression of genes pertaining to Wnt pathway and spermatogenesis by binding to chromatin. In the present study, we delineate the detailed molecular mechanism of Wnt signaling induced mrhl RNA down regulation in mouse spermatogonial cells. Mrhl RNA has an independent transcription unit and our various experiments like Chromatin Immunoprecipitation (in cell line as well as mouse testis) and shRNA mediated down regulation convincingly show that β-catenin and TCF4, which are the key effector proteins of the Wnt signaling pathway are required for down regulation of mrhl RNA. We have identified Ctbp1 as the co-repressor and its occupancy on mrhl RNA promoter depends on both β-catenin and TCF4. Upon Wnt signaling activation, Ctbp1 mediated histone repression marks increase at the mrhl RNA promoter. We also demonstrate that Wnt signaling induced mrhl RNA down regulation results in an up regulation of various meiotic differentiation marker genes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Oxford University Press
ISSN:	0305-1048
Date of Acceptance:	29 September 2015
Last Modified:	01 Nov 2022 10:13
URI:	https://orca.cardiff.ac.uk/id/eprint/90729

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