A U⋅U pair-to-U.C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding
Little is known about how a non-Watson–Crick pair affects the RNA folding dynamics. We studied the effects of a U⋅U-to-U⋅C pair mutation on the folding of a hairpin in human telomerase RNA. The ensemble thermal melting of the hairpins shows an on-pathway intermediate with the disruption of the inter...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2015
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| Online Access: | https://hdl.handle.net/10356/103029 http://hdl.handle.net/10220/25802 |
| _version_ | 1811689390244626432 |
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| author | Zhong, Zhensheng Soh, Lai Huat Lim, Ming Hui Chen, Gang |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Zhong, Zhensheng Soh, Lai Huat Lim, Ming Hui Chen, Gang |
| author_sort | Zhong, Zhensheng |
| collection | NTU |
| description | Little is known about how a non-Watson–Crick pair affects the RNA folding dynamics. We studied the effects of a U⋅U-to-U⋅C pair mutation on the folding of a hairpin in human telomerase RNA. The ensemble thermal melting of the hairpins shows an on-pathway intermediate with the disruption of the internal loop structure containing the U⋅U/U⋅C pairs. By using optical tweezers, we applied a stretching force on the terminal ends of the hairpins to probe directly the non-nearest-neighbour effects upon the mutations. The single U⋅U to U⋅C mutations are observed to 1) lower the mechanical unfolding force by approximately 1 picoNewton (pN) per mutation without affecting the unfolding reaction transition-state position (thus suggesting that removing a single hydrogen bond affects the structural dynamics at least two base pairs away), 2) result in more frequent misfolding into a small hairpin at approximately 10 pN and 3) shift the folding reaction transition-state position towards the native hairpin structure and slightly increase the mechanical folding kinetics (thus suggesting that untrapping from the misfolded state is not the rate-limiting step). |
| first_indexed | 2024-10-01T05:47:20Z |
| format | Journal Article |
| id | ntu-10356/103029 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:47:20Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/1030292020-03-07T12:34:42Z A U⋅U pair-to-U.C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding Zhong, Zhensheng Soh, Lai Huat Lim, Ming Hui Chen, Gang School of Physical and Mathematical Sciences DRNTU::Science::Chemistry::Physical chemistry::Molecular structure and bonding Little is known about how a non-Watson–Crick pair affects the RNA folding dynamics. We studied the effects of a U⋅U-to-U⋅C pair mutation on the folding of a hairpin in human telomerase RNA. The ensemble thermal melting of the hairpins shows an on-pathway intermediate with the disruption of the internal loop structure containing the U⋅U/U⋅C pairs. By using optical tweezers, we applied a stretching force on the terminal ends of the hairpins to probe directly the non-nearest-neighbour effects upon the mutations. The single U⋅U to U⋅C mutations are observed to 1) lower the mechanical unfolding force by approximately 1 picoNewton (pN) per mutation without affecting the unfolding reaction transition-state position (thus suggesting that removing a single hydrogen bond affects the structural dynamics at least two base pairs away), 2) result in more frequent misfolding into a small hairpin at approximately 10 pN and 3) shift the folding reaction transition-state position towards the native hairpin structure and slightly increase the mechanical folding kinetics (thus suggesting that untrapping from the misfolded state is not the rate-limiting step). 2015-06-07T03:39:28Z 2019-12-06T21:04:10Z 2015-06-07T03:39:28Z 2019-12-06T21:04:10Z 2015 2015 Journal Article Zhong, Z., Soh, L. H., Lim, M. H., & Chen, G. (2015). A U⋅U pair-to-U⋅C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding. Chempluschem, 80(8), 1267–1278. 2192-6506 https://hdl.handle.net/10356/103029 http://hdl.handle.net/10220/25802 10.1002/cplu.201500144 en Chempluschem © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| spellingShingle | DRNTU::Science::Chemistry::Physical chemistry::Molecular structure and bonding Zhong, Zhensheng Soh, Lai Huat Lim, Ming Hui Chen, Gang A U⋅U pair-to-U.C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding |
| title | A U⋅U pair-to-U.C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding |
| title_full | A U⋅U pair-to-U.C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding |
| title_fullStr | A U⋅U pair-to-U.C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding |
| title_full_unstemmed | A U⋅U pair-to-U.C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding |
| title_short | A U⋅U pair-to-U.C pair mutation-induced RNA native structure destabilisation and stretching-force-induced RNA misfolding |
| title_sort | u⋅u pair to u c pair mutation induced rna native structure destabilisation and stretching force induced rna misfolding |
| topic | DRNTU::Science::Chemistry::Physical chemistry::Molecular structure and bonding |
| url | https://hdl.handle.net/10356/103029 http://hdl.handle.net/10220/25802 |
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