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

Abstract 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 modulat...

Full description

Bibliographic Details
Main Authors: Olivia S. Rissland, Alexander O. Subtelny, Miranda Wang, Andrew Lugowski, Beth Nicholson, John D. Laver, Sachdev S. Sidhu, Craig A. Smibert, Howard D. Lipshitz, David P. Bartel
Format: Article
Language:English
Published: BMC 2017-10-01
Series:Genome Biology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13059-017-1330-z
id doaj-d95ae799118d42feb5cbf376b05785f8
record_format Article
spelling doaj-d95ae799118d42feb5cbf376b05785f82020-11-25T02:46:31ZengBMCGenome Biology1474-760X2017-10-0118111810.1186/s13059-017-1330-zThe influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexesOlivia S. Rissland0Alexander O. Subtelny1Miranda Wang2Andrew Lugowski3Beth Nicholson4John D. Laver5Sachdev S. Sidhu6Craig A. Smibert7Howard D. Lipshitz8David P. Bartel9Whitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchMolecular Medicine Program, The Hospital for Sick ChildrenMolecular Medicine Program, The Hospital for Sick ChildrenMolecular Medicine Program, The Hospital for Sick ChildrenDepartment of Molecular Genetics, University of TorontoDepartment of Molecular Genetics, University of TorontoDepartment of Molecular Genetics, University of TorontoDepartment of Molecular Genetics, University of TorontoWhitehead Institute for Biomedical ResearchAbstract 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.http://link.springer.com/article/10.1186/s13059-017-1330-zMicroRNAsPoly(A) tailmRNA–protein complexes
collection DOAJ
language English
format Article
sources DOAJ
author Olivia S. Rissland
Alexander O. Subtelny
Miranda Wang
Andrew Lugowski
Beth Nicholson
John D. Laver
Sachdev S. Sidhu
Craig A. Smibert
Howard D. Lipshitz
David P. Bartel
spellingShingle Olivia S. Rissland
Alexander O. Subtelny
Miranda Wang
Andrew Lugowski
Beth Nicholson
John D. Laver
Sachdev S. Sidhu
Craig A. Smibert
Howard D. Lipshitz
David P. Bartel
The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes
Genome Biology
MicroRNAs
Poly(A) tail
mRNA–protein complexes
author_facet Olivia S. Rissland
Alexander O. Subtelny
Miranda Wang
Andrew Lugowski
Beth Nicholson
John D. Laver
Sachdev S. Sidhu
Craig A. Smibert
Howard D. Lipshitz
David P. Bartel
author_sort Olivia S. Rissland
title 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_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_sort influence of micrornas and poly(a) tail length on endogenous mrna–protein complexes
publisher BMC
series Genome Biology
issn 1474-760X
publishDate 2017-10-01
description Abstract 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.
topic MicroRNAs
Poly(A) tail
mRNA–protein complexes
url http://link.springer.com/article/10.1186/s13059-017-1330-z
work_keys_str_mv AT oliviasrissland theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT alexanderosubtelny theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT mirandawang theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT andrewlugowski theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT bethnicholson theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT johndlaver theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT sachdevssidhu theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT craigasmibert theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT howarddlipshitz theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT davidpbartel theinfluenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT oliviasrissland influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT alexanderosubtelny influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT mirandawang influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT andrewlugowski influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT bethnicholson influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT johndlaver influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT sachdevssidhu influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT craigasmibert influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT howarddlipshitz influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
AT davidpbartel influenceofmicrornasandpolyataillengthonendogenousmrnaproteincomplexes
_version_ 1724757838473986048