RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites
Intermolecular RNA-RNA interactions are used by many noncoding RNAs (ncRNAs) to achieve their diverse functions. To aid in identifying these contacts, we developed a method based on RNA Antisense Purification to systematically map RNA-RNA interactions (RAP-RNA) and applied it to investigate two ncRN...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/106849 https://orcid.org/0000-0002-5754-1719 https://orcid.org/0000-0001-5410-7274 |
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| author | Sirokman, Klara McDonel, Patrick Shishkin, Alexander A. Surka, Christine Russell, Pamela Chow, Amy Y. Guttman, Mitchell Lander, Eric Steven Engreitz, Jesse Michael Grossman, Sharon Rachel |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Sirokman, Klara McDonel, Patrick Shishkin, Alexander A. Surka, Christine Russell, Pamela Chow, Amy Y. Guttman, Mitchell Lander, Eric Steven Engreitz, Jesse Michael Grossman, Sharon Rachel |
| author_sort | Sirokman, Klara |
| collection | MIT |
| description | Intermolecular RNA-RNA interactions are used by many noncoding RNAs (ncRNAs) to achieve their diverse functions. To aid in identifying these contacts, we developed a method based on RNA Antisense Purification to systematically map RNA-RNA interactions (RAP-RNA) and applied it to investigate two ncRNAs implicated in RNA processing: U1 snRNA, a component of the spliceosome, and Malat1, a lncRNA that localizes to nuclear speckles. U1 and Malat1 interact with nascent transcripts through distinct targeting mechanisms. Using differential crosslinking, we
confirmed that U1 directly hybridizes to both 5’ splice sites and 5’-splice-site motifs throughout introns and found that Malat1 interacts with pre-mRNAs indirectly through protein intermediates. Interactions with nascent pre-mRNAs cause U1 and Malat1 to localize proximally to chromatin at active genes, demonstrating that ncRNAs can use RNA-RNA interactions to target specific premRNAs and genomic sites. RAP-RNA is sensitive to lower abundance RNAs as well, making it generally applicable for investigating ncRNAs. |
| first_indexed | 2024-09-23T12:28:14Z |
| format | Article |
| id | mit-1721.1/106849 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:28:14Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1068492022-09-28T08:05:52Z RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites Sirokman, Klara McDonel, Patrick Shishkin, Alexander A. Surka, Christine Russell, Pamela Chow, Amy Y. Guttman, Mitchell Lander, Eric Steven Engreitz, Jesse Michael Grossman, Sharon Rachel Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven Engreitz, Jesse Michael Grossman, Sharon Rachel Intermolecular RNA-RNA interactions are used by many noncoding RNAs (ncRNAs) to achieve their diverse functions. To aid in identifying these contacts, we developed a method based on RNA Antisense Purification to systematically map RNA-RNA interactions (RAP-RNA) and applied it to investigate two ncRNAs implicated in RNA processing: U1 snRNA, a component of the spliceosome, and Malat1, a lncRNA that localizes to nuclear speckles. U1 and Malat1 interact with nascent transcripts through distinct targeting mechanisms. Using differential crosslinking, we confirmed that U1 directly hybridizes to both 5’ splice sites and 5’-splice-site motifs throughout introns and found that Malat1 interacts with pre-mRNAs indirectly through protein intermediates. Interactions with nascent pre-mRNAs cause U1 and Malat1 to localize proximally to chromatin at active genes, demonstrating that ncRNAs can use RNA-RNA interactions to target specific premRNAs and genomic sites. RAP-RNA is sensitive to lower abundance RNAs as well, making it generally applicable for investigating ncRNAs. Hertz Foundation American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship Broad Institute of MIT and Harvard 2017-02-03T16:02:47Z 2017-02-03T16:02:47Z 2014-09 2014-06 Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/106849 Engreitz, Jesse M. et al. “RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites.” Cell 159.1 (2014): 188–199. https://orcid.org/0000-0002-5754-1719 https://orcid.org/0000-0001-5410-7274 en_US http://dx.doi.org/10.1016/j.cell.2014.08.018 Cell Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Sirokman, Klara McDonel, Patrick Shishkin, Alexander A. Surka, Christine Russell, Pamela Chow, Amy Y. Guttman, Mitchell Lander, Eric Steven Engreitz, Jesse Michael Grossman, Sharon Rachel RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites |
| title | RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites |
| title_full | RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites |
| title_fullStr | RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites |
| title_full_unstemmed | RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites |
| title_short | RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites |
| title_sort | rna rna interactions enable specific targeting of noncoding rnas to nascent pre mrnas and chromatin sites |
| url | http://hdl.handle.net/1721.1/106849 https://orcid.org/0000-0002-5754-1719 https://orcid.org/0000-0001-5410-7274 |
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