Higher-Order Organization Principles of Pre-translational mRNPs
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UMass Chan Affiliations
Graduate School of Biomedical SciencesDepartment of Biochemistry and Molecular Pharmacology
Program in Systems Biology
RNA Therapeutics Institute
Document Type
Journal ArticlePublication Date
2018-11-15Keywords
Amino Acids, Peptides, and ProteinsBioinformatics
Cell Biology
Cells
Computational Biology
Enzymes and Coenzymes
Molecular Biology
Nucleic Acids, Nucleotides, and Nucleosides
Structural Biology
Systems Biology
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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.Source
Mol Cell. 2018 Nov 15;72(4):715-726.e3. doi: 10.1016/j.molcel.2018.09.012. Epub 2018 Nov 8. Link to article on publisher's site
DOI
10.1016/j.molcel.2018.09.012Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49880PubMed ID
30415953Related Resources
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