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Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity
BACKGROUND: Retrotransposition of mRNA transcripts gives occasionally rise to functional retrogenes. Through acquiring tempero-spatial expression patterns distinct from their parental genes and/or functional mutations in their coding sequences, such retrogenes may in principle reshape signalling net...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831893/ https://www.ncbi.nlm.nih.gov/pubmed/20170508 http://dx.doi.org/10.1186/1471-2148-10-55 |
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author | Zemojtel, Tomasz Duchniewicz, Marlena Zhang, Zhongchun Paluch, Taisa Luz, Hannes Penzkofer, Tobias Scheele, Jürgen S Zwartkruis, Fried JT |
author_facet | Zemojtel, Tomasz Duchniewicz, Marlena Zhang, Zhongchun Paluch, Taisa Luz, Hannes Penzkofer, Tobias Scheele, Jürgen S Zwartkruis, Fried JT |
author_sort | Zemojtel, Tomasz |
collection | PubMed |
description | BACKGROUND: Retrotransposition of mRNA transcripts gives occasionally rise to functional retrogenes. Through acquiring tempero-spatial expression patterns distinct from their parental genes and/or functional mutations in their coding sequences, such retrogenes may in principle reshape signalling networks. RESULTS: Here we present evidence for such a scenario, involving retrogenes of Rap1 belonging to the Ras family of small GTPases. We identified two murine and one human-specific retrogene of Rap1A and Rap1B, which encode proteins that differ by only a few amino acids from their parental Rap1 proteins. Markedly, human hRap1B-retro and mouse mRap1A-retro1 acquired mutations in the 12(th )and 59(th )amino acids, respectively, corresponding to residues mutated in constitutively active oncogenic Ras proteins. Statistical and structural analyses support a functional evolution scenario, where Rap1 isoforms of retrogenic origin are functionally distinct from their parental proteins. Indeed, all retrogene-encoded GTPases have an increased GTP/GDP binding ratio in vivo, indicating that their conformations resemble that of active GTP-bound Rap1. We furthermore demonstrate that these three Rap1 isoforms exhibit distinct affinities for the Ras-binding domain of RalGDS. Finally, when tested for their capacity to induce key cellular processes like integrin-mediated cell adhesion or cell spreading, marked differences are seen. CONCLUSIONS: Together, these data lend strong support for an evolution scenario, where retrotransposition and subsequent mutation events generated species-specific Rap1 isoforms with differential signaling potential. Expression of the constitutively active human Rap1B-retro in cells like those derived from Ramos Burkitt's lymphoma and bone marrow from a patient with myelodysplastic syndrome (MDS) warrants further investigation into its role in disease development. |
format | Text |
id | pubmed-2831893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28318932010-03-04 Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity Zemojtel, Tomasz Duchniewicz, Marlena Zhang, Zhongchun Paluch, Taisa Luz, Hannes Penzkofer, Tobias Scheele, Jürgen S Zwartkruis, Fried JT BMC Evol Biol Research article BACKGROUND: Retrotransposition of mRNA transcripts gives occasionally rise to functional retrogenes. Through acquiring tempero-spatial expression patterns distinct from their parental genes and/or functional mutations in their coding sequences, such retrogenes may in principle reshape signalling networks. RESULTS: Here we present evidence for such a scenario, involving retrogenes of Rap1 belonging to the Ras family of small GTPases. We identified two murine and one human-specific retrogene of Rap1A and Rap1B, which encode proteins that differ by only a few amino acids from their parental Rap1 proteins. Markedly, human hRap1B-retro and mouse mRap1A-retro1 acquired mutations in the 12(th )and 59(th )amino acids, respectively, corresponding to residues mutated in constitutively active oncogenic Ras proteins. Statistical and structural analyses support a functional evolution scenario, where Rap1 isoforms of retrogenic origin are functionally distinct from their parental proteins. Indeed, all retrogene-encoded GTPases have an increased GTP/GDP binding ratio in vivo, indicating that their conformations resemble that of active GTP-bound Rap1. We furthermore demonstrate that these three Rap1 isoforms exhibit distinct affinities for the Ras-binding domain of RalGDS. Finally, when tested for their capacity to induce key cellular processes like integrin-mediated cell adhesion or cell spreading, marked differences are seen. CONCLUSIONS: Together, these data lend strong support for an evolution scenario, where retrotransposition and subsequent mutation events generated species-specific Rap1 isoforms with differential signaling potential. Expression of the constitutively active human Rap1B-retro in cells like those derived from Ramos Burkitt's lymphoma and bone marrow from a patient with myelodysplastic syndrome (MDS) warrants further investigation into its role in disease development. BioMed Central 2010-02-19 /pmc/articles/PMC2831893/ /pubmed/20170508 http://dx.doi.org/10.1186/1471-2148-10-55 Text en Copyright ©2010 Zemojtel et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research article Zemojtel, Tomasz Duchniewicz, Marlena Zhang, Zhongchun Paluch, Taisa Luz, Hannes Penzkofer, Tobias Scheele, Jürgen S Zwartkruis, Fried JT Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity |
title | Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity |
title_full | Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity |
title_fullStr | Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity |
title_full_unstemmed | Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity |
title_short | Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity |
title_sort | retrotransposition and mutation events yield rap1 gtpases with differential signalling capacity |
topic | Research article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831893/ https://www.ncbi.nlm.nih.gov/pubmed/20170508 http://dx.doi.org/10.1186/1471-2148-10-55 |
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