Zaucker, Andreas, Nagorska, Agnieszka, Kumari, Pooja, Hecker, Nikolai, Wang, Ying, Huang, Sizhou, Cooper, Ledean, Sivashanmugam, Lavanya, Vijaykumar, Shruthi, Brosens, Jan J., Gorodkin, Jan and Sampath, Karuna (2018) Translational co-regulation of a ligand and inhibitor by a conserved RNA element. Nucleic Acids Research, 46 (1). pp. 104-119. doi:10.1093/nar/gkx938 ISSN 0305-1048.

Preview	PDF WRAP-translational-co-regulation-ligand-inhibitor-conserved-RNA-Sampath-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4Mb) | Preview
	PDF WRAP-translational-co-regulation-ligand-inhibitor-conserved-RNA-element-Sampath-2017.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (1250Kb)

Request Changes to record.

Abstract

In many organisms, transcriptional and post-transcriptional regulation of components of pathways or processes has been reported. However, to date, there are few reports of translational co-regulation of multiple components of a developmental signaling pathway. Here, we show that an RNA element which we previously identified as a dorsal localization element (DLE) in the 3′UTR of zebrafish nodal-related1/squint (ndr1/sqt) ligand mRNA, is shared by the related ligand nodal-related2/cyclops (ndr2/cyc) and the nodal inhibitors, lefty1 (lft1) and lefty2 mRNAs. We investigated the activity of the DLEs through functional assays in live zebrafish embryos. The lft1 DLE localizes fluorescently labeled RNA similarly to the ndr1/sqt DLE. Similar to the ndr1/sqt 3′UTR, the lft1 and lft2 3′UTRs are bound by the RNA-binding protein (RBP) and translational repressor, Y-box binding protein 1 (Ybx1), whereas deletions in the DLE abolish binding to Ybx1. Analysis of zebrafish ybx1 mutants shows that Ybx1 represses lefty1 translation in embryos. CRISPR/Cas9-mediated inactivation of human YBX1 also results in human NODAL translational de-repression, suggesting broader conservation of the DLE RNA element/Ybx1 RBP module in regulation of Nodal signaling. Our findings demonstrate translational co-regulation of components of a signaling pathway by an RNA element conserved in both sequence and structure and an RBP, revealing a ‘translational regulon’.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Non-coding RNA, RNA-protein interactions, Nucleic acids
Journal or Publication Title:	Nucleic Acids Research
Publisher:	Oxford University Press
ISSN:	0305-1048
Official Date:	9 January 2018
Dates:	Date Event 9 January 2018 Published 20 October 2017 Available 3 October 2017 Accepted
Volume:	46
Number:	1
Page Range:	pp. 104-119
DOI:	10.1093/nar/gkx938
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	12 October 2017
Date of first compliant Open Access:	5 April 2018
Funder:	University of Warwick Research Development Fund, Midlands Integrative Biosciences Training Partnership (MIBTP), Lundbeck Foundation, Innovationsfonden [Innovation Fund Denmark]
Grant number:	R77-A6365 (Lundbeck Foundation) ; 0603-00320 (Innovationsfonden)
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED Warwick Medical School http://dx.doi.org/10.13039/501100004443 UNSPECIFIED [BBSRC] Biotechnology and Biological Sciences Research Council http://dx.doi.org/10.13039/501100000268 UNSPECIFIED [HEFCE] Higher Education Funding Council for England http://dx.doi.org/10.13039/100011722
Related URLs:	Publisher

Request changes or add full text files to a record

Repository staff actions (login required)

View Item

Downloads