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| Status |
Public on Dec 01, 2022 |
| Title |
Structural features within the NORAD long noncoding RNA underlie efficient repression of Pumilio activity |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
It is increasingly appreciated that long non-coding RNAs (lncRNAs) carry out important functions in mammalian cells, but how these are encoded in their sequences, and manifested in their structures remains largely unknown. Some lncRNAs bind to and modulate the availability of RNA binding proteins, but the structural principles that underlie this mode of regulation are underexplored. Here, we focused on the NORAD lncRNA, which binds Pumilio proteins and modulates their ability to repress hundreds of mRNA targets. We probed the RNA structure and long-range RNA-RNA interactions formed by NORAD inside cells, under different stressful conditions. We discovered that NORAD structure is highly modular, and consists of well-defined domains that contribute independently to NORAD function. The structure adopted by NORAD spatially clusters the Pumilio binding sites along NORAD in a manner that contributes to de-repression of Pumilio target proteins. Following arsenite stress, the majority of NORAD structure undergoes relaxation and forms inter-molecular interactions with RNAs that are targeted to stress granules. NORAD sequence thus dictates elaborated structural domain organisation that facilitates its function on multiple levels, and which helps explain the extensive evolutionary sequence conservation of NORAD regions that are not predicted to directly bind Pumilio proteins.
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| Overall design |
Examination of NORAD RNA structure in: untreated cells (3 biological replicates and 3 paired controls); cells under DNA damage stress (2 biological replicates and 2 paired controls; and cells under Arsenite stress (3 biological replicates and 3 paired controls)
DMS-seq for a region comprising NRU7-8 in NORAD
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| Contributor(s) |
Ziv O, Farberov S, Lau JY, Miska E, Kudla G, Ulitsky I |
| Citation missing |
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| Submission date |
Nov 08, 2021 |
| Last update date |
Mar 06, 2024 |
| Contact name |
Grzegorz Kudla |
| E-mail(s) |
gkudla@gmail.com
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| Phone |
+44 (0) 131 332 2471
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| Organization name |
University of Edinburgh
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| Department |
MRC HGU
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| Street address |
Crewe Road
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| City |
Edinburgh |
| ZIP/Postal code |
EH4 2XU |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (31)
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| GSM5683130 |
NORAD Arsenite replicate1 |
| GSM5683131 |
NORAD Arsenite replicate2 |
| GSM5683132 |
NORAD Arsenite replicate3 |
| GSM5683133 |
NORAD Doxocyclin replicate1 |
| GSM5683134 |
NORAD Doxocyclin replicate2 |
| GSM5683135 |
NORAD Control replicate1 |
| GSM5683136 |
NORAD Control replicate2 |
| GSM5683137 |
NORAD Control replicate3 |
| GSM5683138 |
NORAD Arsenite Control replicate1 |
| GSM5683139 |
NORAD Arsenite Control replicate2 |
| GSM5683140 |
NORAD Arsenite Control replicate3 |
| GSM5683141 |
NORAD Doxocyclin Control replicate1 |
| GSM5683142 |
NORAD Doxocyclin Control replicate2 |
| GSM8127864 |
control, amplicon A (DMS-seq) |
| GSM8127865 |
control, amplicon B (DMS-seq) |
| GSM8127866 |
Delta-disordered (DMS-seq) |
| GSM8127867 |
mini-NORAD7/8, rep1, amplicon A (DMS-seq) |
| GSM8127868 |
mini-NORAD7/8, rep1, amplicon B (DMS-seq) |
| GSM8127869 |
mini-NORAD7/8, rep2, amplicon A (DMS-seq) |
| GSM8127870 |
mini-NORAD7/8, rep2, amplicon B (DMS-seq) |
| GSM8127871 |
Full NORAD OE, amplicon A (DMS-seq) |
| GSM8127872 |
Full NORAD OE, amplicon B (DMS-seq) |
| GSM8127873 |
alt. sequence1, amplicon A (DMS-seq) |
| GSM8127874 |
alt. sequence1, amplicon B (DMS-seq) |
| GSM8127875 |
alt. sequence2, amplicon A (DMS-seq) |
| GSM8127876 |
alt. sequence2, amplicon B (DMS-seq) |
| GSM8127877 |
Endogenous, amplicon A (DMS-seq) |
| GSM8127878 |
Endogenous, amplicon B (DMS-seq) |
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| Relations |
| BioProject |
PRJNA778798 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE188445_RAW.tar |
78.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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