Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units
Long non-coding RNAs (lncRNAs) can perform a variety of key cellular functions by interacting with proteins and other RNAs. Recent studies have shown that the functions of lncRNAS are largely mediated by their structures. However, our structural knowledge for most lncRNAS is limited to sequence-base...
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doaj-a71dfe91939a4518b00565169dde46a42021-06-09T05:57:34ZengElsevierComputational and Structural Biotechnology Journal2001-03702021-01-011932453254Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat unitsUciel Chorostecki0Ester Saus1Toni Gabaldón2Barcelona Supercomputing Centre (BSC-CNS). Jordi Girona, 29. 08034 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, SpainBarcelona Supercomputing Centre (BSC-CNS). Jordi Girona, 29. 08034 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, SpainBarcelona Supercomputing Centre (BSC-CNS). Jordi Girona, 29. 08034 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain; Corresponding author at: Barcelona Supercomputing Centre (BSC-CNS). Jordi Girona, 29. 08034 Barcelona, Spain.Long non-coding RNAs (lncRNAs) can perform a variety of key cellular functions by interacting with proteins and other RNAs. Recent studies have shown that the functions of lncRNAS are largely mediated by their structures. However, our structural knowledge for most lncRNAS is limited to sequence-based computational predictions. Non-coding RNA activated by DNA damage (NORAD) is an atypical lncRNA due to its abundant expression and high sequence conservation. NORAD regulates genomic stability by interacting with proteins and microRNAs. Previous sequence-based characterization has identified a modular organization of NORAD composed of several NORAD repeat units (NRUs). These units comprise the protein-binding elements and are separated by regular spacers. Here, we experimentally determine for the first time the secondary structure of NORAD using the nextPARS approach. Our results suggest that the spacer regions provide structural stability to NRUs. Furthermore, we uncover two previously unreported NRUs, and determine the core structural motifs conserved across NRUs. Overall, these findings will help to elucidate the function and evolution of NORAD.http://www.sciencedirect.com/science/article/pii/S2001037021002269Long non-coding RNAsNORADRNA structureProbing RNAncRNAs |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Uciel Chorostecki Ester Saus Toni Gabaldón |
spellingShingle |
Uciel Chorostecki Ester Saus Toni Gabaldón Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units Computational and Structural Biotechnology Journal Long non-coding RNAs NORAD RNA structure Probing RNA ncRNAs |
author_facet |
Uciel Chorostecki Ester Saus Toni Gabaldón |
author_sort |
Uciel Chorostecki |
title |
Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units |
title_short |
Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units |
title_full |
Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units |
title_fullStr |
Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units |
title_full_unstemmed |
Structural characterization of NORAD reveals a stabilizing role of spacers and two new repeat units |
title_sort |
structural characterization of norad reveals a stabilizing role of spacers and two new repeat units |
publisher |
Elsevier |
series |
Computational and Structural Biotechnology Journal |
issn |
2001-0370 |
publishDate |
2021-01-01 |
description |
Long non-coding RNAs (lncRNAs) can perform a variety of key cellular functions by interacting with proteins and other RNAs. Recent studies have shown that the functions of lncRNAS are largely mediated by their structures. However, our structural knowledge for most lncRNAS is limited to sequence-based computational predictions. Non-coding RNA activated by DNA damage (NORAD) is an atypical lncRNA due to its abundant expression and high sequence conservation. NORAD regulates genomic stability by interacting with proteins and microRNAs. Previous sequence-based characterization has identified a modular organization of NORAD composed of several NORAD repeat units (NRUs). These units comprise the protein-binding elements and are separated by regular spacers. Here, we experimentally determine for the first time the secondary structure of NORAD using the nextPARS approach. Our results suggest that the spacer regions provide structural stability to NRUs. Furthermore, we uncover two previously unreported NRUs, and determine the core structural motifs conserved across NRUs. Overall, these findings will help to elucidate the function and evolution of NORAD. |
topic |
Long non-coding RNAs NORAD RNA structure Probing RNA ncRNAs |
url |
http://www.sciencedirect.com/science/article/pii/S2001037021002269 |
work_keys_str_mv |
AT ucielchorostecki structuralcharacterizationofnoradrevealsastabilizingroleofspacersandtwonewrepeatunits AT estersaus structuralcharacterizationofnoradrevealsastabilizingroleofspacersandtwonewrepeatunits AT tonigabaldon structuralcharacterizationofnoradrevealsastabilizingroleofspacersandtwonewrepeatunits |
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