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The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function

TRIM-NHL proteins are conserved regulators of development and differentiation but their molecular function has remained largely elusive. Here, we report an as yet unrecognized activity for the mammalian TRIM-NHL protein TRIM71 as a repressor of mRNAs. We show that TRIM71 is associated with mRNAs and...

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Autores principales: Loedige, Inga, Gaidatzis, Dimos, Sack, Ragna, Meister, Gunter, Filipowicz, Witold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592402/
https://www.ncbi.nlm.nih.gov/pubmed/23125361
http://dx.doi.org/10.1093/nar/gks1032
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author Loedige, Inga
Gaidatzis, Dimos
Sack, Ragna
Meister, Gunter
Filipowicz, Witold
author_facet Loedige, Inga
Gaidatzis, Dimos
Sack, Ragna
Meister, Gunter
Filipowicz, Witold
author_sort Loedige, Inga
collection PubMed
description TRIM-NHL proteins are conserved regulators of development and differentiation but their molecular function has remained largely elusive. Here, we report an as yet unrecognized activity for the mammalian TRIM-NHL protein TRIM71 as a repressor of mRNAs. We show that TRIM71 is associated with mRNAs and that it promotes translational repression and mRNA decay. We have identified Rbl1 and Rbl2, two transcription factors whose down-regulation is important for stem cell function, as TRIM71 targets in mouse embryonic stem cells. Furthermore, one of the defining features of TRIM-NHL proteins, the NHL domain, is necessary and sufficient to target TRIM71 to RNA, while the RING domain that confers ubiquitin ligase activity is dispensable for repression. Our results reveal strong similarities between TRIM71 and Drosophila BRAT, the best-studied TRIM-NHL protein and a well-documented translational repressor, suggesting that BRAT and TRIM71 are part of a family of mRNA repressors regulating proliferation and differentiation.
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spelling pubmed-35924022013-03-08 The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function Loedige, Inga Gaidatzis, Dimos Sack, Ragna Meister, Gunter Filipowicz, Witold Nucleic Acids Res RNA TRIM-NHL proteins are conserved regulators of development and differentiation but their molecular function has remained largely elusive. Here, we report an as yet unrecognized activity for the mammalian TRIM-NHL protein TRIM71 as a repressor of mRNAs. We show that TRIM71 is associated with mRNAs and that it promotes translational repression and mRNA decay. We have identified Rbl1 and Rbl2, two transcription factors whose down-regulation is important for stem cell function, as TRIM71 targets in mouse embryonic stem cells. Furthermore, one of the defining features of TRIM-NHL proteins, the NHL domain, is necessary and sufficient to target TRIM71 to RNA, while the RING domain that confers ubiquitin ligase activity is dispensable for repression. Our results reveal strong similarities between TRIM71 and Drosophila BRAT, the best-studied TRIM-NHL protein and a well-documented translational repressor, suggesting that BRAT and TRIM71 are part of a family of mRNA repressors regulating proliferation and differentiation. Oxford University Press 2013-01 2012-11-02 /pmc/articles/PMC3592402/ /pubmed/23125361 http://dx.doi.org/10.1093/nar/gks1032 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
spellingShingle RNA
Loedige, Inga
Gaidatzis, Dimos
Sack, Ragna
Meister, Gunter
Filipowicz, Witold
The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function
title The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function
title_full The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function
title_fullStr The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function
title_full_unstemmed The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function
title_short The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function
title_sort mammalian trim-nhl protein trim71/lin-41 is a repressor of mrna function
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592402/
https://www.ncbi.nlm.nih.gov/pubmed/23125361
http://dx.doi.org/10.1093/nar/gks1032
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