Biology subjects

Namkoong, S.

Publications and source records attributed to Namkoong, S..

3 recordsLinked to original sources

bioRxiv2022

m6a governs length-dependent enrichment of mRNAs in stress granules

Stress granules are biomolecular condensates composed of protein and mRNA. Long mRNAs are enriched in stress granules, which is thought to reflect the ability of long mRNAs to form multiple RNA-RNA interactions with other mRNAs. RNA-RNA interactions are thus thought to be critical for stress granule formation. Stress granule-enriched mRNAs also often contain multiple N6-methyladenosine (m6A) residues. YTHDF proteins bind m6A, creating mRNA-protein complexes that partition into stress granules. Here we determine the basis of length-dependent enrichment of mRNAs in stress granules. We show that depletion of m6A is sufficient to abrogate the length-dependent enrichment of mRNAs in stress granules. We show that the presence of m6A predicts which mRNAs are enriched. m6A formation is triggered by long exons, which are often found in long mRNAs, accounting for the link between m6A, length and stress granule enrichment. Thus, length-dependent enrichment of mRNAs in stress granules is driven by YTHDF-mRNA interactions.

molecular biology↗

bioRxiv2020

Lopinavir-ritonavir is not an effective inhibitor of the main protease activity of SARS-CoV-2 in vitro

COVID-19 has caused over 900,000 deaths worldwide as of September 2020, and effective medicines are urgently needed. Lopinavir was identified as an inhibitor of the HIV protease, and a lopinavir-ritonavir combination therapy was reported to be beneficial for the treatment of SARS and MERS. However, recent clinical tests could not prove that lopinavir-ritonavir therapy was an effective treatment for COVID-19. In this report, we examined the effect of lopinavir and ritonavir to the activity of the purified main protease (Mpro) protein of SARS- CoV-2, the causative virus of COVID-19. Unexpectedly, lopinavir and ritonavir did not inhibit Mpro activity. These results will aid the drug candidate selection for ongoing and future COVID-19 clinical trials.

microbiology↗

bioRxiv2019

Heterogeneous transcriptome response to DNA damage at single cell resolution.

Cancer cells often heterogeneously respond to genotoxic chemotherapy, leading to fractional killing and chemoresistance1, 2, which remain as the major obstacles in cancer treatment. It is widely believed that DNA damage induces a uniform response in regulating transcription and that cell fate is passively determined by a threshold mechanism evaluating the level of transcriptional responses3. On the contrary to this assumption, here we show that a surprisingly high level of heterogeneity exists in individual cell transcriptome responses to DNA damage, and that these transcriptome variations dictate the cell fate after DNA damage. Many DNA damage response genes, including tumor suppressor p53 targets, were exclusively expressed in only a subset of cells having specific cell fate, producing unique stress responses tailored for the fate that the cells are committed to. For instance, CDKN1A, the best known p53 target inhibiting cell cycle, was specifically expressed in a subset of cells undergoing cell cycle checkpoint, while other pro-apoptotic p53 targets were expressed only in cells undergoing apoptosis. A small group of cells exhibited neither checkpoint nor apoptotic responses, but produced a unique transcriptional program that conferred strong chemoresistance to the cells. The heterogeneous transcriptome response to DNA damage was also observed at the protein level in flow cytometry. Our results demonstrate that cell fate heterogeneity after DNA damage is mediated by distinct transcriptional programs generating fate-specific gene expression landscapes. This finding provides an important insight into understanding heterogeneous chemotherapy responses of cancer cells.

cell biology↗