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A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins
Cytoplasmic changes in polyA tail length is a key mechanism of translational control and is implicated in germline development, synaptic plasticity, cellular proliferation, senescence, and cancer progression. The presence of a U-rich cytoplasmic polyadenylation element (CPE) in the 3′ untranslated r...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083092/ https://www.ncbi.nlm.nih.gov/pubmed/24990967 http://dx.doi.org/10.1101/gad.241133.114 |
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author | Afroz, Tariq Skrisovska, Lenka Belloc, Eulàlia Guillén-Boixet, Jordina Méndez, Raúl Allain, Frédéric H.-T. |
author_facet | Afroz, Tariq Skrisovska, Lenka Belloc, Eulàlia Guillén-Boixet, Jordina Méndez, Raúl Allain, Frédéric H.-T. |
author_sort | Afroz, Tariq |
collection | PubMed |
description | Cytoplasmic changes in polyA tail length is a key mechanism of translational control and is implicated in germline development, synaptic plasticity, cellular proliferation, senescence, and cancer progression. The presence of a U-rich cytoplasmic polyadenylation element (CPE) in the 3′ untranslated regions (UTRs) of the responding mRNAs gives them the selectivity to be regulated by the CPE-binding (CPEB) family of proteins, which recognizes RNA via the tandem RNA recognition motifs (RRMs). Here we report the solution structures of the tandem RRMs of two human paralogs (CPEB1 and CPEB4) in their free and RNA-bound states. The structures reveal an unprecedented arrangement of RRMs in the free state that undergo an original closure motion upon RNA binding that ensures high fidelity. Structural and functional characterization of the ZZ domain (zinc-binding domain) of CPEB1 suggests a role in both protein–protein and protein–RNA interactions. Together with functional studies, the structures reveal how RNA binding by CPEB proteins leads to an optimal positioning of the N-terminal and ZZ domains at the 3′ UTR, which favors the nucleation of the functional ribonucleoprotein complexes for translation regulation. |
format | Online Article Text |
id | pubmed-4083092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40830922015-01-01 A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins Afroz, Tariq Skrisovska, Lenka Belloc, Eulàlia Guillén-Boixet, Jordina Méndez, Raúl Allain, Frédéric H.-T. Genes Dev Research Paper Cytoplasmic changes in polyA tail length is a key mechanism of translational control and is implicated in germline development, synaptic plasticity, cellular proliferation, senescence, and cancer progression. The presence of a U-rich cytoplasmic polyadenylation element (CPE) in the 3′ untranslated regions (UTRs) of the responding mRNAs gives them the selectivity to be regulated by the CPE-binding (CPEB) family of proteins, which recognizes RNA via the tandem RNA recognition motifs (RRMs). Here we report the solution structures of the tandem RRMs of two human paralogs (CPEB1 and CPEB4) in their free and RNA-bound states. The structures reveal an unprecedented arrangement of RRMs in the free state that undergo an original closure motion upon RNA binding that ensures high fidelity. Structural and functional characterization of the ZZ domain (zinc-binding domain) of CPEB1 suggests a role in both protein–protein and protein–RNA interactions. Together with functional studies, the structures reveal how RNA binding by CPEB proteins leads to an optimal positioning of the N-terminal and ZZ domains at the 3′ UTR, which favors the nucleation of the functional ribonucleoprotein complexes for translation regulation. Cold Spring Harbor Laboratory Press 2014-07-01 /pmc/articles/PMC4083092/ /pubmed/24990967 http://dx.doi.org/10.1101/gad.241133.114 Text en © 2014 Afroz et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Afroz, Tariq Skrisovska, Lenka Belloc, Eulàlia Guillén-Boixet, Jordina Méndez, Raúl Allain, Frédéric H.-T. A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins |
title | A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins |
title_full | A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins |
title_fullStr | A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins |
title_full_unstemmed | A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins |
title_short | A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins |
title_sort | fly trap mechanism provides sequence-specific rna recognition by cpeb proteins |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083092/ https://www.ncbi.nlm.nih.gov/pubmed/24990967 http://dx.doi.org/10.1101/gad.241133.114 |
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