Translation is required for miRNA‐dependent decay of endogenous transcripts
| Autor: | Adriano Biasini, Constance Ciaudo, Harry Wischnewski, Jennifer Y. Tan, Stefano de Pretis, René Dreos, Rajika Arora, Ana C. Marques, Mattia Pelizzola, Baroj Abdulkarim |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
RNA Stability
translation Endogeny Biology Ribosome Article General Biochemistry Genetics and Molecular Biology Cell Line Mice 03 medical and health sciences 0302 clinical medicine Genes Reporter microRNA Gene expression RNA metabolic labelling Animals Gene silencing RNA Messenger Dicer knockout mESC long noncoding RNAs Molecular Biology Gene Psychological repression miRNA 030304 developmental biology 0303 health sciences General Immunology and Microbiology Sequence Analysis RNA General Neuroscience High-Throughput Nucleotide Sequencing Mouse Embryonic Stem Cells Translation (biology) Articles Protein Biosynthesis & Quality Control RNA Biology Artificial Gene Fusion 3. Good health Cell biology MicroRNAs Gene Expression Regulation Protein Biosynthesis RNA Long Noncoding Ribosomes 030217 neurology & neurosurgery |
| Zdroj: | The EMBO Journal, 40 (3) The EMBO Journal |
| Popis: | Post‐transcriptional repression of gene expression by miRNAs occurs through transcript destabilization or translation inhibition. mRNA decay is known to account for most miRNA‐dependent repression. However, because transcript decay occurs co‐translationally, whether target translation is a requirement for miRNA‐dependent transcript destabilization remains unknown. To decouple these two molecular processes, we used cytosolic long noncoding RNAs (lncRNAs) as models for endogenous transcripts that are not translated. We show that, despite interacting with the miRNA‐loaded RNA‐induced silencing complex, the steady‐state abundance and decay rates of these transcripts are minimally affected by miRNA loss. To further validate the apparent requirement of translation for miRNA‐dependent decay, we fused two lncRNA candidates to the 3’‐end of a protein‐coding gene reporter and found this results in their miRNA‐dependent destabilization. Further analysis revealed that the few natural lncRNAs whose levels are regulated by miRNAs in mESCs tend to associate with translating ribosomes, and possibly represent misannotated micropeptides, further substantiating the necessity of target translation for miRNA‐dependent transcript decay. In summary, our analyses suggest that translation is required for miRNA‐dependent transcript destabilization, and demonstrate that the levels of coding and noncoding transcripts are differently affected by miRNAs. Real lncRNAs are bound, but not degraded by miRNA‐loaded RNA‐induced silencing complexes, establishing different susceptibilities of coding and non‐coding RNA to miRNA‐dependent repression. |
| Databáze: | OpenAIRE |
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