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| Status |
Public on Feb 05, 2019 |
| Title |
Gene expression profiles in Norad+/+ and Norad-/- brains and spleens [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Although numerous long noncoding RNAs (lncRNAs) have been identified, our understanding of their roles in mammalian physiology remains limited. Here we investigated the physiologic function of the conserved lncRNA Norad in vivo. Deletion of Norad in mice results in genomic instability and mitochondrial dysfunction, leading to a dramatic multi-system degenerative phenotype resembling premature aging. Loss of tissue homeostasis in Norad-deficient animals is attributable to augmented activity of PUMILIO proteins, which act as post-transcriptional repressors of target mRNAs to which they bind. Norad is the preferred RNA target of PUMILIO2 (PUM2) in mouse tissues and, upon loss of Norad, PUM2 hyperactively represses key genes required for mitosis and mitochondrial function. Accordingly, enforced Pum2 expression fully phenocopies Norad deletion, resulting in rapid-onset aging-associated phenotypes. These findings provide new insights and open new lines of investigation into the roles of noncoding RNAs and RNA binding proteins in normal physiology and aging.
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| Overall design |
Gene expression profiles were determined by RNA-seq.
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| Contributor(s) |
Kopp F, Chen B, Zhang H, Lee S, Xie Y, Mendell JT |
| Citation(s) |
30735131 |
| |
| Submission date |
Oct 23, 2018 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Joshua Mendell |
| E-mail(s) |
joshua.mendell@utsouthwestern.edu
|
| Organization name |
UT Southwestern Medical Center
|
| Department |
Molecular Biology
|
| Street address |
6000 Harry Hines Blvd., NA6.200A
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9148 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA498098 |
| SRA |
SRP166551 |
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