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Translational control of leftright patterning by a 3’UTR RNA element
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Nagorska, Agnieszka (2022) Translational control of leftright patterning by a 3’UTR RNA element. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3909613
Abstract
Heart development is a dynamic process that occurs rapidly in zebrafish embryos. Within 48 hpf heart looping is complete with the formation of two distinct chambers. During the next 5 days of development, endocardial cushions begin differentiating into mature heart valves that help to regulate the blood flow in zebrafish. Previous studies in mice and zebrafish have shown that pro-protein convertase FurinA has a role in cardiac morphogenesis. To date, the zebrafish genome has not been well annotated leaving sequences of many transcripts and their isoforms unknown. Here I describe a novel furina transcript X1, which interestingly has an unusually long 3’UTR sequence. The alternative 3’UTR furina isoform is expressed at embryonic stages prior to organ positioning. Computational analysis of the zebrafish transcriptome shows that a short sequence motif ‘AGCAC’ and a stem loop which we had previously studied in the 3’UTR of Nodal ligand sqt and inhibitors lefty1 and lefty2, is present in a variant 3’UTR transcript of furina. Reporter localization assays show that the furina 3'UTR element behaves similarly to the other 3’UTR motifs identified in the Nodal pathway. It also forms complexes in vivo with the RNA-binding protein and translational repressor, Ybx1. Analysis of the ybx1 mutant embryos revealed that they manifest leftright asymmetry and cardiac morphogenesis defects. I observed that the atrioventricular canal in these mutants is significantly larger than in the wild type controls. In a proportion of ybx1 mutant embryos, as a result of an enlargement of their atrioventricular canal, there is retrograde blood flow at the 5 dpf. In this work, I show an essential function for the 3’UTR element/Ybx1 regulon in translational repression of FurinA and reveal a new upstream regulatory mechanism that controls embryonic left-right asymmetry and heart development in zebrafish embryos.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QL Zoology Q Science > QP Physiology |
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Library of Congress Subject Headings (LCSH): | Zebra danio, Zebra danio -- Embryology, Morphogenesis, Heart -- Development, Messenger RNA, Genetic translation | ||||
Official Date: | August 2022 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Sampath, Karuna, 1967- | ||||
Sponsors: | Warwick Medical School ; Medical and Life Sciences Research Fund | ||||
Format of File: | |||||
Extent: | xi, 157 pages : colour illustrations | ||||
Language: | eng |
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