The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis
Telomerase RNA (TR) provides the template for DNA repeat synthesis at telomeres and is essential for genome stability in continuously dividing cells. We mapped the RNA interactome of human TR (hTR) and identified a set of non-coding and coding hTR-interacting RNAs, including the histone 1C mRNA (HIS...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/88999 http://hdl.handle.net/10220/47009 |
| _version_ | 1826114082238889984 |
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| author | Ivanyi-Nagy, Roland Ahmed, Syed Moiz Peter, Sabrina Ramani, Priya Dharshana Ong, Peh Fern Dreesen, Oliver Dröge, Peter |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Ivanyi-Nagy, Roland Ahmed, Syed Moiz Peter, Sabrina Ramani, Priya Dharshana Ong, Peh Fern Dreesen, Oliver Dröge, Peter |
| author_sort | Ivanyi-Nagy, Roland |
| collection | NTU |
| description | Telomerase RNA (TR) provides the template for DNA repeat synthesis at telomeres and is essential for genome stability in continuously dividing cells. We mapped the RNA interactome of human TR (hTR) and identified a set of non-coding and coding hTR-interacting RNAs, including the histone 1C mRNA (HIST1H1C). Disruption of the hTR-HIST1H1C RNA association resulted in markedly increased telomere elongation without affecting telomerase enzymatic activity. Conversely, over-expression of HIST1H1C led to telomere attrition. By using a combination of mutations to disentangle the effects of histone 1 RNA synthesis, protein expression, and hTR interaction, we show that HIST1H1C RNA negatively regulates telomere length independently of its protein coding potential. Taken together, our data provide important insights into a surprisingly complex hTR-RNA interaction network and define an unexpected non-coding RNA role for HIST1H1C in regulating telomere length homeostasis, thus offering a glimpse into the mostly uncharted, vast space of non-canonical messenger RNA functions. |
| first_indexed | 2024-10-01T03:33:22Z |
| format | Journal Article |
| id | ntu-10356/88999 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:33:22Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/889992023-02-28T17:01:24Z The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis Ivanyi-Nagy, Roland Ahmed, Syed Moiz Peter, Sabrina Ramani, Priya Dharshana Ong, Peh Fern Dreesen, Oliver Dröge, Peter School of Biological Sciences NTU Institute of Structural Biology DRNTU::Science::Biological sciences Homeostasis Telomerase RNA Telomerase RNA (TR) provides the template for DNA repeat synthesis at telomeres and is essential for genome stability in continuously dividing cells. We mapped the RNA interactome of human TR (hTR) and identified a set of non-coding and coding hTR-interacting RNAs, including the histone 1C mRNA (HIST1H1C). Disruption of the hTR-HIST1H1C RNA association resulted in markedly increased telomere elongation without affecting telomerase enzymatic activity. Conversely, over-expression of HIST1H1C led to telomere attrition. By using a combination of mutations to disentangle the effects of histone 1 RNA synthesis, protein expression, and hTR interaction, we show that HIST1H1C RNA negatively regulates telomere length independently of its protein coding potential. Taken together, our data provide important insights into a surprisingly complex hTR-RNA interaction network and define an unexpected non-coding RNA role for HIST1H1C in regulating telomere length homeostasis, thus offering a glimpse into the mostly uncharted, vast space of non-canonical messenger RNA functions. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Published version 2018-12-17T07:41:33Z 2019-12-06T17:15:35Z 2018-12-17T07:41:33Z 2019-12-06T17:15:35Z 2018 Journal Article Ivanyi-Nagy, R., Ahmed, S. M., Peter, S., Ramani, P. D., Ong, P. F., Dreesen, O., & Dröge, P. (2018). The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis. eLife, 7, e40037-. doi: 10.7554/eLife.40037 https://hdl.handle.net/10356/88999 http://hdl.handle.net/10220/47009 10.7554/eLife.40037 en eLife © 2018 Ivanyi-Nagy et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. 30 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Homeostasis Telomerase RNA Ivanyi-Nagy, Roland Ahmed, Syed Moiz Peter, Sabrina Ramani, Priya Dharshana Ong, Peh Fern Dreesen, Oliver Dröge, Peter The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis |
| title | The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis |
| title_full | The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis |
| title_fullStr | The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis |
| title_full_unstemmed | The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis |
| title_short | The RNA interactome of human telomerase RNA reveals a coding-independent role for a histone mRNA in telomere homeostasis |
| title_sort | rna interactome of human telomerase rna reveals a coding independent role for a histone mrna in telomere homeostasis |
| topic | DRNTU::Science::Biological sciences Homeostasis Telomerase RNA |
| url | https://hdl.handle.net/10356/88999 http://hdl.handle.net/10220/47009 |
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