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...

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Bibliographic Details
Main Authors: Wang, Miranda, Lugowski, Andrew, Nicholson, Beth, Laver, John D., Sidhu, Sachdev S., Smibert, Craig A., Lipshitz, Howard D., Subtelny, Alexander Orest, Rissland, Olivia S., Bartel, David
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Published: Biomed Central Ltd. 2018
Online Access:http://hdl.handle.net/1721.1/116461
https://orcid.org/0000-0001-5029-5909
https://orcid.org/0000-0002-3872-2856
Description
Summary: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.