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NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif

The RNA-binding protein nuclear factor 90 (NF90) has been implicated in the stabilization, transport and translational control of several target mRNAs. However, a systematic analysis of NF90 target mRNAs has not been performed. Here, we use ribonucleoprotein immunoprecipitation analysis to identify...

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Detalles Bibliográficos
Autores principales: Kuwano, Yuki, Pullmann, Rudolf, Marasa, Bernard S., Abdelmohsen, Kotb, Lee, Eun Kyung, Yang, Xiaoling, Martindale, Jennifer L., Zhan, Ming, Gorospe, Myriam
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800222/
https://www.ncbi.nlm.nih.gov/pubmed/19850717
http://dx.doi.org/10.1093/nar/gkp861
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author Kuwano, Yuki
Pullmann, Rudolf
Marasa, Bernard S.
Abdelmohsen, Kotb
Lee, Eun Kyung
Yang, Xiaoling
Martindale, Jennifer L.
Zhan, Ming
Gorospe, Myriam
author_facet Kuwano, Yuki
Pullmann, Rudolf
Marasa, Bernard S.
Abdelmohsen, Kotb
Lee, Eun Kyung
Yang, Xiaoling
Martindale, Jennifer L.
Zhan, Ming
Gorospe, Myriam
author_sort Kuwano, Yuki
collection PubMed
description The RNA-binding protein nuclear factor 90 (NF90) has been implicated in the stabilization, transport and translational control of several target mRNAs. However, a systematic analysis of NF90 target mRNAs has not been performed. Here, we use ribonucleoprotein immunoprecipitation analysis to identify a large subset of NF90-associated mRNAs. Comparison of the 3′-untranslated regions (UTRs) of these mRNAs led to the elucidation of a 25- to 30-nucleotide, RNA signature motif rich in adenines and uracils. Insertion of the AU-rich NF90 motif (‘NF90m’) in the 3′UTR of an EGFP heterologous reporter did not affect the steady-state level of the chimeric EGFP-NF90m mRNA or its cytosolic abundance. Instead, the translation of EGFP-NF90m mRNA was specifically repressed in an NF90-dependent manner, as determined by analysing nascent EGFP translation, the distribution of chimeric mRNAs on polysome gradients and the steady-state levels of expressed EGFP protein. The interaction of endogenous NF90 with target mRNAs was validated after testing both endogenous mRNAs and recombinant biotinylated transcripts containing NF90 motif hits. Further analysis showed that the stability of endogenous NF90 target mRNAs was not significantly influenced by NF90 abundance, while their translation increased when NF90 levels were reduced. In summary, we have identified an AU-rich RNA motif present in NF90 target mRNAs and have obtained evidence that NF90 represses the translation of this subset of mRNAs.
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spelling pubmed-28002222009-12-31 NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif Kuwano, Yuki Pullmann, Rudolf Marasa, Bernard S. Abdelmohsen, Kotb Lee, Eun Kyung Yang, Xiaoling Martindale, Jennifer L. Zhan, Ming Gorospe, Myriam Nucleic Acids Res RNA The RNA-binding protein nuclear factor 90 (NF90) has been implicated in the stabilization, transport and translational control of several target mRNAs. However, a systematic analysis of NF90 target mRNAs has not been performed. Here, we use ribonucleoprotein immunoprecipitation analysis to identify a large subset of NF90-associated mRNAs. Comparison of the 3′-untranslated regions (UTRs) of these mRNAs led to the elucidation of a 25- to 30-nucleotide, RNA signature motif rich in adenines and uracils. Insertion of the AU-rich NF90 motif (‘NF90m’) in the 3′UTR of an EGFP heterologous reporter did not affect the steady-state level of the chimeric EGFP-NF90m mRNA or its cytosolic abundance. Instead, the translation of EGFP-NF90m mRNA was specifically repressed in an NF90-dependent manner, as determined by analysing nascent EGFP translation, the distribution of chimeric mRNAs on polysome gradients and the steady-state levels of expressed EGFP protein. The interaction of endogenous NF90 with target mRNAs was validated after testing both endogenous mRNAs and recombinant biotinylated transcripts containing NF90 motif hits. Further analysis showed that the stability of endogenous NF90 target mRNAs was not significantly influenced by NF90 abundance, while their translation increased when NF90 levels were reduced. In summary, we have identified an AU-rich RNA motif present in NF90 target mRNAs and have obtained evidence that NF90 represses the translation of this subset of mRNAs. Oxford University Press 2010-01 2009-10-22 /pmc/articles/PMC2800222/ /pubmed/19850717 http://dx.doi.org/10.1093/nar/gkp861 Text en Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Kuwano, Yuki
Pullmann, Rudolf
Marasa, Bernard S.
Abdelmohsen, Kotb
Lee, Eun Kyung
Yang, Xiaoling
Martindale, Jennifer L.
Zhan, Ming
Gorospe, Myriam
NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif
title NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif
title_full NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif
title_fullStr NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif
title_full_unstemmed NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif
title_short NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif
title_sort nf90 selectively represses the translation of target mrnas bearing an au-rich signature motif
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800222/
https://www.ncbi.nlm.nih.gov/pubmed/19850717
http://dx.doi.org/10.1093/nar/gkp861
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