Control of transcription elongation and DNA repair by alarmone ppGpp.

Second messenger (p)ppGpp (collectively guanosine tetraphosphate and guanosine pentaphosphate) mediates bacterial adaptation to nutritional stress by modulating transcription initiation. More recently, ppGpp has been implicated in coupling transcription and DNA repair; however, the mechanism of ppGpp engagement remained elusive. Here we present structural, biochemical and genetic evidence that ppGpp controls Escherichia coli RNA polymerase (RNAP) during elongation via a specific site that is nonfunctional during initiation.

Plant polysaccharides with anti-lung injury effects as a potential therapeutic strategy for COVID-19.

When coronavirus disease 2019 (COVID-19) develops into the severe phase, lung injury, acute respiratory distress syndrome, and/or respiratory failure could develop within a few days. As a result of pulmonary tissue injury, pathomorphological changes usually present endothelial dysfunction, inflammatory cell infiltration of the lung interstitium, defective gas exchange, and wall leakage. Consequently, COVID-19 may progress to tremendous lung injury, ongoing lung failure, and death.

Principles of RNA and nucleotide discrimination by the RNA processing enzyme RppH.

All enzymes face a challenge of discriminating cognate substrates from similar cellular compounds. Finding a correct substrate is especially difficult for the Escherichia coli Nudix hydrolase RppH, which triggers 5'-end-dependent RNA degradation by removing orthophosphate from the 5'-diphosphorylated transcripts. Here we show that RppH binds and slowly hydrolyzes NTPs, NDPs and (p)ppGpp, which each resemble the 5'-end of RNA.

The crystal structure of Zika virus NS5 reveals conserved drug targets.

Zika virus (ZIKV) has emerged as major health concern, as ZIKV infection has been shown to be associated with microcephaly, severe neurological disease and possibly male sterility. As the largest protein component within the ZIKV replication complex, NS5 plays key roles in the life cycle and survival of the virus through its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains. Here, we present the crystal structures of ZIKV NS5 MTase in complex with an RNA cap analogue (GpppA) and the free NS5 RdRp.