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Series GSE44746 Query DataSets for GSE44746
Status Public on Nov 06, 2014
Title Loss of cytosine-5 methylation in tRNA triggers stress responses in a disease model for Intellectual Disability
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
Other
Summary Mutations in the cytosine-5 RNA methyltransferase NSun2 can cause Intellectual Disability (ID) and symptoms commonly found in patients with Dubowitz syndrome. By analysing gene expression data with the global cytosine-5 RNA methylome in NSun2-deficient mice, we find that loss of cytosine-5 RNA methylation increases the fragmentation of transfer RNAs (tRNA) leading to an accumulation of 5’ halves. Cleavage of tRNAs by Angiogenin is a common cellular stress response to silence translational programmes, and we show that Angiogenin binds tRNAs lacking site-specific NSun2-methylation with higher affinity. Furthermore, cells lacking functional NSun2 up-regulate stress markers, and deletion of NSun2 compromises cellular survival in response stress stimuli including UV-light and oxidative stress. The decreased tolerance of NSun2 null cells towards oxidative stress can be rescued through inhibition of Angiogenin. In conclusion, cytosine-5 RNA methylation is an essential post-transcriptional mechanism during cellular stress responses and NSun2-mediated tRNA methylation protects from Angiogenin-dependent stress-induced RNA cleavage.
 
Overall design RNA Methylation profiling by high throughput sequencing
small non-coding RNA profiling by high throughput sequencing
Pol III Chromatin-IP profiling by high throughput sequencing
 
Contributor(s) Blanco S
Citation(s) 25063673
Submission date Feb 28, 2013
Last update date May 15, 2019
Contact name Patrick Lombard
E-mail(s) pdl30@cam.ac.uk
Organization name University of Cambridge
Street address Tennis Court Road, Cambridge
City Cambridge
State/province Cambridgeshire
ZIP/Postal code CB21QR
Country United Kingdom
 
Platforms (1)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
Samples (21)
GSM1090034 Wt_rep1 [do1661_unk_skin_unk_mmuWT#1_CRI01]
GSM1090035 Wt_rep2 [do1662_unk_skin_unk_mmuWT#2_CRI01]
GSM1090036 Wt_rep3 [do1663_unk_skin_unk_mmuWT#3_CRI01]
Relations
BioProject PRJNA191532
SRA SRP019226

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE44746_RAW.tar 16.3 Mb (http)(custom) TAR (of TXT)
GSE44746_polIII.counts.txt.gz 27.9 Kb (ftp)(http) TXT
GSE44746_trna.counts.txt.gz 927.1 Kb (ftp)(http) TXT
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Processed data provided as supplementary file
Raw data are available in SRA
Processed data are available on Series record
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