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Series GSE165202 Query DataSets for GSE165202
Status Public on Jul 01, 2021
Title Neuronal Nsun2 deficiency is associated with codon-specific epitranscriptomic dysregulation of Gly-tRNAs and corresponding proteomic shift impacting synaptic signaling and behavior
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Other
Summary Epitranscriptomic mechanisms linking the brain proteome to cognition and complex behaviors essentially remain unexplored. Here, we describe bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of NOL1/NOP2/SUN domain 2 (Nsun2) in the prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a sharp drop in tRNA m5C levels, resulting in significant deficits in expression of 70% (7/10) of tRNAGlyGCC, GlyCCC GlyTCC isodecoders, while expression changes in non-glycinergic tRNAs were minimal (4/152). Altogether, 1488/5820 proteins were sensitive to neuronal Nsun2-deficiency, in conjunction with GCC and CCC codon-specific defects in translational efficiencies and loss of Gly-rich proteins critical for glutamatergic neurotransmission, resulting in impaired synaptic signaling at PFC pyramidal neurons and impairments in contextual fear memory. These distortions in the neuronal translatome were associated with an adaptive, 2.46-fold up-regulation in PFC glycine levels with increased expression of multiple enzymes in the glycine biosynthetic pathway. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC and link synaptic plasticity and complex behaviors to epitranscriptomic regulation of cognate tRNAs and the proteomic homeostasis associated with specific amino acids.
 
Overall design mRNA and small RNA profiles of adult Nsun2 KO and WT cortex
 
Contributor(s) Blaze J, Akbarian S
Citation(s) 34389722, 34880236
Submission date Jan 20, 2021
Last update date Jan 10, 2022
Contact name Jennifer Blaze
E-mail(s) jennifer.blaze@mssm.edu
Organization name Icahn School of Medicine at Mount Sinai
Street address 1470 Madison Ave 9-202
City New York
State/province New York
ZIP/Postal code 10029
Country USA
 
Platforms (4)
GPL16417 Illumina MiSeq (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (103)
GSM5028198 wild type 1- cortex
GSM5028199 wild type 2- cortex
GSM5028200 Nsun2 KO 1- cortex
Relations
BioProject PRJNA693540
SRA SRP302576

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
GSE165202_HydrotRNAseq_processed_data.xlsx 26.2 Kb (ftp)(http) XLSX
GSE165202_RAW.tar 477.8 Mb (http)(custom) TAR (of TDF)
GSE165202_Riboseq_processed_data.xlsx 1.6 Mb (ftp)(http) XLSX
GSE165202_YAMATseq_processed_data.xlsx 32.4 Kb (ftp)(http) XLSX
GSE165202_tRF_seq_processed_data.xlsx 153.6 Kb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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