Project description:COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infected >200 million people resulting in >4 million deaths. However, temporal landscape of the SARS-CoV-2 translatome and its impact on the human genome remain unexplored. Here, we report a high-resolution atlas of the translatome and transcriptome of SARS-CoV-2 for various time points after infecting human cells. Intriguingly, substantial amount of SARS-CoV-2 translation initiates at a novel translation initiation site (TIS) located in the leader sequence, termed TIS-L. Since TIS-L is included in all the genomic and subgenomic RNAs, the SARS-CoV-2 translatome may be regulated by a sophisticated interplay between TIS-L and downstream TISs. TIS-L functions as a strong translation enhancer for ORF S, and as translation suppressors for most of the other ORFs. Our global temporal atlas provides compelling insight into unique regulation of the SARS-CoV-2 translatome and helps comprehensively evaluate its impact on the human genome.
Project description:Functional specification of mammalian tissues is a result of precise regulation of gene expression during development. Although previous transcriptomic and proteomic analyses have provided great biological insight into tissue specific gene expression and their physiological relevance in development, our understanding of translational regulation in developing tissues is lacking. Here, we report a spatio-temporally resolved translatome analysis of six mouse tissues at embryonic and adult stages to quantify the effects of translational regulation and identify new translational components. We quantified the spatial and temporal divergence of gene expression and showed specific changes in gene expression and pathways underlying the divergence. We further showed dynamic translational control by modulating translational efficiency, enhancing tissue specificity during development. We discovered thousands of actively translated upstream open read frames (ORFs) that exhibited spatio-temporal patterns and demonstrated their regulatory roles in translational regulation. Finally, we identified known and novel micropeptides encoded by small ORFs from long non-coding RNAs with functional relevance to tissue development. Our data and analyses facilitate a better understanding of complex translational regulation across tissue and developmental spectra and serve as a useful resource of mouse translatome.
Project description:High-temporal resolution profiling was performed on U2OS fibroblasts to detect rhythmic transcripts Keywords: time course Samples were collected every hour for 48 hours from dexamethasone-synchronized U2OS cells. Cells synchronized with dexamethasone for 24 hours, and harvested from the 24th to 71st hour. Samples were analyzed using Affymetrix arrays.
Project description:High-temporal resolution profiling was performed on mouse liver to detect rhythmic transcripts Experiment Overall Design: Samples were collected every hour for 48 hours from 3-5 mice per time point from liver. Samples were pooled and analyzed using Affymetrix arrays.