Higher-Order Organization Principles of Pre-translational mRNPs
Name
nihms-1510438.pdf
Description
Accepted version
Size
2.95 MB
Format
Adobe PDF
Checksum (MD5)
387da29ef822e9b90ad1456f98e75bee
Author(s)
Imakaev, Maksim Viktorovich
Mirny, Leonid A
Date Issued
November 2018
Journal
Molecular cell
Publisher
Elsevier BV
Citation
Metkar, Mihir et al. “Higher-Order Organization Principles of Pre-translational mRNPs.” Molecular cell, vol. 72, no. 4, 2018, pp. 715-726.e3 © 2018 The Author(s)
Version
Author's final manuscript
Abstract
Compared to noncoding RNAs (ncRNAs), such as rRNAs and ribozymes, for which high-resolution structures abound, little is known about the tertiary structures of mRNAs. In eukaryotic cells, newly made mRNAs are packaged with proteins in highly compacted mRNA particles (mRNPs), but the manner of this mRNA compaction is unknown. Here, we developed and implemented RIPPLiT (RNA immunoprecipitation and proximity ligation in tandem), a transcriptome-wide method for probing the 3D conformations of RNAs stably associated with defined proteins, in this case, exon junction complex (EJC) core factors. EJCs multimerize with other mRNP components to form megadalton-sized complexes that protect large swaths of newly synthesized mRNAs from endonuclease digestion. Unlike ncRNPs, wherein strong locus-specific structures predominate, mRNPs behave more like flexible polymers. Polymer analysis of proximity ligation data for hundreds of mRNA species demonstrates that nascent and pre-translational mammalian mRNAs are compacted by their associated proteins into linear rod-like structures. Metkar et al. developed a new toolkit, a biochemical approach, RIPPLiT and a bioinformatics suite to capture and analyze higher-order organization of RNPs. They were able to enrich for interactions within mRNAs and further, using polymer analysis on 100 s of mRNAs, identified a unifying principle for mRNP packaging.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2018.09.012
