Higher-Order Organization Principles of Pre-translational mRNPs
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 m...
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/126169 |
| _version_ | 1826208778351017984 |
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| author | Imakaev, Maksim Viktorovich Mirny, Leonid A |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Imakaev, Maksim Viktorovich Mirny, Leonid A |
| author_sort | Imakaev, Maksim Viktorovich |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:12:30Z |
| format | Article |
| id | mit-1721.1/126169 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:12:30Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1261692022-10-01T19:45:47Z Higher-Order Organization Principles of Pre-translational mRNPs Imakaev, Maksim Viktorovich Mirny, Leonid A Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Physics 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. 2020-07-14T12:02:57Z 2020-07-14T12:02:57Z 2018-11 2019-12-10T13:22:29Z Article http://purl.org/eprint/type/JournalArticle 1097-2765 https://hdl.handle.net/1721.1/126169 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) en 10.1016/J.MOLCEL.2018.09.012 Molecular cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Imakaev, Maksim Viktorovich Mirny, Leonid A Higher-Order Organization Principles of Pre-translational mRNPs |
| title | Higher-Order Organization Principles of Pre-translational mRNPs |
| title_full | Higher-Order Organization Principles of Pre-translational mRNPs |
| title_fullStr | Higher-Order Organization Principles of Pre-translational mRNPs |
| title_full_unstemmed | Higher-Order Organization Principles of Pre-translational mRNPs |
| title_short | Higher-Order Organization Principles of Pre-translational mRNPs |
| title_sort | higher order organization principles of pre translational mrnps |
| url | https://hdl.handle.net/1721.1/126169 |
| work_keys_str_mv | AT imakaevmaksimviktorovich higherorderorganizationprinciplesofpretranslationalmrnps AT mirnyleonida higherorderorganizationprinciplesofpretranslationalmrnps |