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Series GSE143277 Query DataSets for GSE143277
Status Public on Jan 09, 2020
Title Translation is required for miRNA-dependent decay of endogenous transcripts.
Organism Mus musculus
Experiment type Non-coding RNA profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Posttranscriptional repression by microRNA (miRNA) occurs through transcript destabilization or translation inhibition. Whereas RNA degradation explains most miRNA-dependent repression, transcript decay occurs co-translationally, raising questions regarding the requirement of target translation to miRNA-dependent transcript destabilization. To assess the contribution of translation to miRNA-mediated RNA destabilization, we decoupled these two molecular processes by dissecting the impact of miRNA loss of function on cytosolic long noncoding RNAs (lncRNAs). We show, that despite interacting with miRNA loaded RNA-induced silencing complex (miRISC), the steady state abundance and degradation rates of these endogenously expressed non-translated transcripts are minimally impacted by miRNA loss. To validate the requirement of translation to miRNA-dependent decay, we fused a miRISC bound lncRNA, whose levels are unaffected by miRNAs, to the 3’end of a protein-coding gene reporter and shown that this results in its miRNA-dependent transcript destabilization. Furthermore, analysis of the few lncRNAs whose levels are regulated by miRNAs revealed these tend to associate with translating ribosomes and are likely misannotated micropeptides, further substantiating the necessity of target translation to miRNA-dependent transcript decay. Our analyses revealed the strict requirement of translation for miRNA-dependent transcript destabilization and demonstrates that the levels of coding and noncoding transcripts are differently affected by miRNAs. 
Overall design Conditional loss of dicer function was induced in mESCs and small RNA sequencing as well as mRNA metabolic labelling was performed to assess changes in transcript degradation and miRNA loss, between wild-type and Dicer depleted mESCs.
Contributor(s) Biasini A, de Pretis S, Tan JY, Abdulkarim B, Wischnewski H, Dreos R, Pelizzola M, Ciaudo C, Marques AC
Citation(s) 33300180, 35459101
Submission date Jan 08, 2020
Last update date May 05, 2022
Contact name Ana Marques
Organization name University of Lausanne
Department Department of Computational Biology
Street address Rue du Bugnon 27
City Lausanne
ZIP/Postal code 1005
Country Switzerland
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (31)
GSM4255946 mESCs, smallRNA_KO_d0_1
GSM4255947 mESCs, smallRNA_KO_d0_2
GSM4255948 mESCs, smallRNA_KO_d0_3
BioProject PRJNA599577
SRA SRP240275

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Supplementary file Size Download File type/resource
GSE143277_4sU_TPM_table.txt.gz 6.7 Mb (ftp)(http) TXT
GSE143277_smallRNAseq_counts_table.txt.gz 21.1 Kb (ftp)(http) TXT
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