RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus that causes the respiratory disease known as coronavirus disease 2019 (COVID-19). Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the signal recognition particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses.
Assuntos
COVID-19/metabolismo , Interações Hospedeiro-Patógeno , Biossíntese de Proteínas , Splicing de RNA , SARS-CoV-2/metabolismo , Proteínas não Estruturais Virais/metabolismo , Células A549 , Animais , COVID-19/virologia , Chlorocebus aethiops , Células HEK293 , Humanos , Interferons/metabolismo , Transporte Proteico , RNA Mensageiro/metabolismo , RNA Ribossômico 18S/metabolismo , RNA Citoplasmático Pequeno/química , RNA Citoplasmático Pequeno/metabolismo , Partícula de Reconhecimento de Sinal/química , Partícula de Reconhecimento de Sinal/metabolismo , Células Vero , Proteínas não Estruturais Virais/químicaRESUMO
Transposable elements (TEs) have profoundly affected the evolution of transcriptional and chromatin profiles in mammalian genomes. In a recent paper, Percharde et al. (2018) identify a lncRNA-like function for LINE1 transposable elements in regulating gene expression to facilitate embryonic stem cell self-renewal and preimplantation development.
Assuntos
Elementos de DNA Transponíveis , RNA Longo não Codificante , Animais , Evolução Molecular , Expressão GênicaRESUMO
The human response to serious cutaneous damage is limited to relatively primitive wound healing, whereby collagenous scar tissue fills the wound bed. Scars assure structural integrity at the expense of functional regeneration. In contrast, axolotls have the remarkable capacity to functionally regenerate full thickness wounds. Here, we identified a novel role for SALL4 in regulating collagen transcription after injury that is essential for perfect skin regeneration in axolotl. Furthermore, we identify miR-219 as a molecular regulator of Sall4 during wound healing. Taken together, our work highlights one molecular mechanism that allows for efficient cutaneous wound healing in the axolotl.