Cargando…

The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes

BACKGROUND: All mRNAs are bound in vivo by proteins to form mRNA–protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the a...

Descripción completa

Detalles Bibliográficos
Autores principales: Rissland, Olivia S., Subtelny, Alexander O., Wang, Miranda, Lugowski, Andrew, Nicholson, Beth, Laver, John D., Sidhu, Sachdev S., Smibert, Craig A., Lipshitz, Howard D., Bartel, David P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664449/
https://www.ncbi.nlm.nih.gov/pubmed/29089021
http://dx.doi.org/10.1186/s13059-017-1330-z
_version_ 1783275000776622080
author Rissland, Olivia S.
Subtelny, Alexander O.
Wang, Miranda
Lugowski, Andrew
Nicholson, Beth
Laver, John D.
Sidhu, Sachdev S.
Smibert, Craig A.
Lipshitz, Howard D.
Bartel, David P.
author_facet Rissland, Olivia S.
Subtelny, Alexander O.
Wang, Miranda
Lugowski, Andrew
Nicholson, Beth
Laver, John D.
Sidhu, Sachdev S.
Smibert, Craig A.
Lipshitz, Howard D.
Bartel, David P.
author_sort Rissland, Olivia S.
collection PubMed
description BACKGROUND: All mRNAs are bound in vivo by proteins to form mRNA–protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in human cells. RESULTS: Despite the transient nature of repressed intermediates, we detect significant changes in mRNP composition, marked by dissociation of eIF4G and PABP, and by recruitment of DDX6. Furthermore, although poly(A)-tail length has been considered critical in post-transcriptional regulation, differences in steady-state tail length explain little of the variation in either PABP association or mRNP organization more generally. Instead, relative occupancy of core components correlates best with gene expression. CONCLUSIONS: These results indicate that posttranscriptional regulatory factors, such as microRNAs, influence the associations of PABP and other core factors, and do so without substantially affecting steady-state tail length. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-017-1330-z) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5664449
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-56644492017-11-08 The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes Rissland, Olivia S. Subtelny, Alexander O. Wang, Miranda Lugowski, Andrew Nicholson, Beth Laver, John D. Sidhu, Sachdev S. Smibert, Craig A. Lipshitz, Howard D. Bartel, David P. Genome Biol Research BACKGROUND: All mRNAs are bound in vivo by proteins to form mRNA–protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in human cells. RESULTS: Despite the transient nature of repressed intermediates, we detect significant changes in mRNP composition, marked by dissociation of eIF4G and PABP, and by recruitment of DDX6. Furthermore, although poly(A)-tail length has been considered critical in post-transcriptional regulation, differences in steady-state tail length explain little of the variation in either PABP association or mRNP organization more generally. Instead, relative occupancy of core components correlates best with gene expression. CONCLUSIONS: These results indicate that posttranscriptional regulatory factors, such as microRNAs, influence the associations of PABP and other core factors, and do so without substantially affecting steady-state tail length. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-017-1330-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-31 /pmc/articles/PMC5664449/ /pubmed/29089021 http://dx.doi.org/10.1186/s13059-017-1330-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Rissland, Olivia S.
Subtelny, Alexander O.
Wang, Miranda
Lugowski, Andrew
Nicholson, Beth
Laver, John D.
Sidhu, Sachdev S.
Smibert, Craig A.
Lipshitz, Howard D.
Bartel, David P.
The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes
title The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes
title_full The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes
title_fullStr The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes
title_full_unstemmed The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes
title_short The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes
title_sort influence of micrornas and poly(a) tail length on endogenous mrna–protein complexes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664449/
https://www.ncbi.nlm.nih.gov/pubmed/29089021
http://dx.doi.org/10.1186/s13059-017-1330-z
work_keys_str_mv AT risslandolivias theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT subtelnyalexandero theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT wangmiranda theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT lugowskiandrew theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT nicholsonbeth theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT laverjohnd theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT sidhusachdevs theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT smibertcraiga theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT lipshitzhowardd theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT barteldavidp theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT risslandolivias influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT subtelnyalexandero influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT wangmiranda influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT lugowskiandrew influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT nicholsonbeth influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT laverjohnd influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT sidhusachdevs influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT smibertcraiga influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT lipshitzhowardd influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT barteldavidp influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes