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Series GSE188445 Query DataSets for GSE188445
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
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.
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
Contributor(s) Ziv O, Farberov S, Lau JY, Miska E, Kudla G, Ulitsky I
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Submission date Nov 08, 2021
Last update date Mar 06, 2024
Contact name Grzegorz Kudla
Phone +44 (0) 131 332 2471
Organization name University of Edinburgh
Department MRC HGU
Street address Crewe Road
City Edinburgh
ZIP/Postal code EH4 2XU
Country United Kingdom
Platforms (2)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (31)
GSM5683127 NORAD replicate1
GSM5683128 NORAD replicate2
GSM5683129 NORAD replicate3
BioProject PRJNA778798

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Supplementary file Size Download File type/resource
GSE188445_RAW.tar 78.5 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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