A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival
Functions of many long noncoding RNAs (lncRNAs) depend on their ability to interact with multiple copies of specific RNA-binding proteins (RBPs). Here, we devised a workflow combining bioinformatics and experimental validation steps to systematically identify RNAs capable of multivalent RBP recruitm...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2019
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/87602 http://hdl.handle.net/10220/50329 |
| _version_ | 1826129361072291840 |
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| author | Tan, Jason S. C. Yap, Karen Mukhina, Svetlana Zhang, Gen Ong, Hong Sheng Makeyev, Eugene V. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Tan, Jason S. C. Yap, Karen Mukhina, Svetlana Zhang, Gen Ong, Hong Sheng Makeyev, Eugene V. |
| author_sort | Tan, Jason S. C. |
| collection | NTU |
| description | Functions of many long noncoding RNAs (lncRNAs) depend on their ability to interact with multiple copies of specific RNA-binding proteins (RBPs). Here, we devised a workflow combining bioinformatics and experimental validation steps to systematically identify RNAs capable of multivalent RBP recruitment. This uncovered a number of previously unknown transcripts encoding high-density RBP recognition arrays within genetically normal short tandem repeats. We show that a top-scoring hit in this screen, lncRNA PNCTR, contains hundreds of pyrimidine tract-binding protein (PTBP1)-specific motifs allowing it to sequester a substantial fraction of PTBP1 in a nuclear body called perinucleolar compartment. Importantly, PNCTR is markedly overexpressed in a variety of cancer cells and its downregulation is sufficient to induce programmed cell death at least in part by stimulating PTBP1 splicing regulation activity. This work expands our understanding of the repeat-containing fraction of the human genome and illuminates a novel mechanism driving malignant transformation of cancer cells. |
| first_indexed | 2024-10-01T07:39:18Z |
| format | Journal Article |
| id | ntu-10356/87602 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:39:18Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/876022023-02-28T17:02:07Z A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival Tan, Jason S. C. Yap, Karen Mukhina, Svetlana Zhang, Gen Ong, Hong Sheng Makeyev, Eugene V. School of Biological Sciences Long Noncoding RNA Short Tandem Repeats Science::Biological sciences Functions of many long noncoding RNAs (lncRNAs) depend on their ability to interact with multiple copies of specific RNA-binding proteins (RBPs). Here, we devised a workflow combining bioinformatics and experimental validation steps to systematically identify RNAs capable of multivalent RBP recruitment. This uncovered a number of previously unknown transcripts encoding high-density RBP recognition arrays within genetically normal short tandem repeats. We show that a top-scoring hit in this screen, lncRNA PNCTR, contains hundreds of pyrimidine tract-binding protein (PTBP1)-specific motifs allowing it to sequester a substantial fraction of PTBP1 in a nuclear body called perinucleolar compartment. Importantly, PNCTR is markedly overexpressed in a variety of cancer cells and its downregulation is sufficient to induce programmed cell death at least in part by stimulating PTBP1 splicing regulation activity. This work expands our understanding of the repeat-containing fraction of the human genome and illuminates a novel mechanism driving malignant transformation of cancer cells. NMRC (Natl Medical Research Council, S’pore) Published version 2019-11-05T01:49:53Z 2019-12-06T16:45:25Z 2019-11-05T01:49:53Z 2019-12-06T16:45:25Z 2018 Journal Article Yap, K., Mukhina, S., Zhang, G., Tan, J. S. C., Ong, H. S., & Makeyev, E. V. (2018). A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survivall. Molecular Cell, 72(3), 525-540. doi:10.1016/j.molcel.2018.08.041 1097-2765 https://hdl.handle.net/10356/87602 http://hdl.handle.net/10220/50329 10.1016/j.molcel.2018.08.041 en Molecular Cell © 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 29 p. application/pdf |
| spellingShingle | Long Noncoding RNA Short Tandem Repeats Science::Biological sciences Tan, Jason S. C. Yap, Karen Mukhina, Svetlana Zhang, Gen Ong, Hong Sheng Makeyev, Eugene V. A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival |
| title | A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival |
| title_full | A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival |
| title_fullStr | A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival |
| title_full_unstemmed | A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival |
| title_short | A short tandem repeat-enriched RNA assembles a nuclear compartment to control alternative splicing and promote cell survival |
| title_sort | short tandem repeat enriched rna assembles a nuclear compartment to control alternative splicing and promote cell survival |
| topic | Long Noncoding RNA Short Tandem Repeats Science::Biological sciences |
| url | https://hdl.handle.net/10356/87602 http://hdl.handle.net/10220/50329 |
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