Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD
In the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), expansion of the G4C2 hexanucleotide repeat in the gene C9orf72 is a most common known cause of the disease. Here we use atomic force microscopy (AFM) and gel electrophoresis to visualize the fo...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/162435 |
| _version_ | 1811680440783732736 |
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| author | Bose, Krishnashish Maity, Arijit Ngo, Khac Huy Vandana, J. Jeya Shneider, Neil A. Phan, Anh Tuân |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Bose, Krishnashish Maity, Arijit Ngo, Khac Huy Vandana, J. Jeya Shneider, Neil A. Phan, Anh Tuân |
| author_sort | Bose, Krishnashish |
| collection | NTU |
| description | In the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), expansion of the G4C2 hexanucleotide repeat in the gene C9orf72 is a most common known cause of the disease. Here we use atomic force microscopy (AFM) and gel electrophoresis to visualize the formation of higher-order structures by RNA G4C2 repeats in physiologically relevant conditions. For the RNA sequence r[G4C2G4], we observed G-wires with left-handed undulating features of 4.4-nm periodicity and a uniform height which is consistently higher than that of a duplex B-DNA. These higher-order structures were not degraded fully when treated with a mixture of RNase A and RNase T1. Similarly, higher-order structures were observed for sequences containing three or four G4C2 repeats, pointing towards their potential formation in longer sequence contexts. Our observations suggest that RNA G-quadruplex blocks and G-wires can accumulate in cells containing G4C2 repeat transcripts. |
| first_indexed | 2024-10-01T03:25:05Z |
| format | Journal Article |
| id | ntu-10356/162435 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:25:05Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1624352022-10-19T02:01:13Z Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD Bose, Krishnashish Maity, Arijit Ngo, Khac Huy Vandana, J. Jeya Shneider, Neil A. Phan, Anh Tuân School of Physical and Mathematical Sciences NTU Institute of Structural Biology Science::Biological sciences G-Quadruplex C9ORF72 In the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), expansion of the G4C2 hexanucleotide repeat in the gene C9orf72 is a most common known cause of the disease. Here we use atomic force microscopy (AFM) and gel electrophoresis to visualize the formation of higher-order structures by RNA G4C2 repeats in physiologically relevant conditions. For the RNA sequence r[G4C2G4], we observed G-wires with left-handed undulating features of 4.4-nm periodicity and a uniform height which is consistently higher than that of a duplex B-DNA. These higher-order structures were not degraded fully when treated with a mixture of RNase A and RNase T1. Similarly, higher-order structures were observed for sequences containing three or four G4C2 repeats, pointing towards their potential formation in longer sequence contexts. Our observations suggest that RNA G-quadruplex blocks and G-wires can accumulate in cells containing G4C2 repeat transcripts. Ministry of Education (MOE) Nanyang Technological University This research was supported by Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2015-T2-1-092) and grants from Nanyang Technological University to A.T.P. 2022-10-19T02:01:12Z 2022-10-19T02:01:12Z 2022 Journal Article Bose, K., Maity, A., Ngo, K. H., Vandana, J. J., Shneider, N. A. & Phan, A. T. (2022). Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD. Biochemical and Biophysical Research Communications, 610, 113-118. https://dx.doi.org/10.1016/j.bbrc.2022.03.162 0006-291X https://hdl.handle.net/10356/162435 10.1016/j.bbrc.2022.03.162 35462091 2-s2.0-85128702532 610 113 118 en MOE2015-T2-1-092 Biochemical and Biophysical Research Communications © 2022 Elsevier Inc. All rights reserved. |
| spellingShingle | Science::Biological sciences G-Quadruplex C9ORF72 Bose, Krishnashish Maity, Arijit Ngo, Khac Huy Vandana, J. Jeya Shneider, Neil A. Phan, Anh Tuân Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD |
| title | Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD |
| title_full | Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD |
| title_fullStr | Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD |
| title_full_unstemmed | Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD |
| title_short | Formation of RNA G-wires by G₄C₂ repeats associated with ALS and FTD |
| title_sort | formation of rna g wires by g₄c₂ repeats associated with als and ftd |
| topic | Science::Biological sciences G-Quadruplex C9ORF72 |
| url | https://hdl.handle.net/10356/162435 |
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