RNA 5'-modification with NAD+/NADH (oxidized/reduced nicotinamide adenine dinucleotide) has been found in bacteria, eukaryotes and viruses. 5'-NAD is incorporated into RNA by RNA polymerases (RNAPs) during the initiation of synthesis. It is unknown (i) which factors and physiological conditions permit substantial NAD incorporation into RNA in vivo and (ii) how 5'-NAD impacts gene expression and the fate of RNA in bacteria. Here we show in Escherichia coli that RNA NADylation is stimulated by low cellular concentration of the competing substrate ATP, and by weakening ATP contacts with RNAP active site. Additionally, RNA NADylation may be influenced by DNA supercoiling. RNA NADylation does not interfere with posttranscriptional RNA processing by major ribonuclease RNase E. It does not impact the base-pairing between RNAI, the repressor of plasmid replication, and its antisense target, RNAII. Leaderless NADylated model mRNA cI-lacZ is recognized by the 70S ribosome and is translated with the same efficiency as triphosphorylated cI-lacZ mRNA. Translation exposes the 5'-NAD of this mRNA to de-capping by NudC enzyme. We suggest that NADylated mRNAs are rapidly degraded, consistent with their low abundance in published datasets. Furthermore, we observed that ppGpp inhibits NudC de-capping activity, contributing to the growth phase-dependency of NADylated RNA levels.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• bakteriální RNA metabolismus   genetika   MeSH
• DNA řízené RNA-polymerasy metabolismus   genetika   MeSH
• endoribonukleasy metabolismus   genetika   MeSH
• Escherichia coli * genetika   metabolismus   MeSH
• messenger RNA metabolismus   genetika   MeSH
• NAD * metabolismus   MeSH
• posttranskripční úpravy RNA MeSH
• proteiny z Escherichia coli metabolismus   genetika   MeSH
• proteosyntéza MeSH
• RNA čepičky * metabolismus   MeSH
• stochastické procesy MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosintrifosfát MeSH
• bakteriální RNA MeSH
• DNA řízené RNA-polymerasy MeSH
• endoribonukleasy MeSH
• messenger RNA MeSH
• NAD * MeSH
• proteiny z Escherichia coli MeSH
• ribonuclease E MeSH Prohlížeč
• RNA čepičky * MeSH

Among the ~22,000 human genes, very few remain that have unknown functions. One such example is suprabasin (SBSN). Originally described as a component of the cornified envelope, the function of stratified epithelia-expressed SBSN is unknown. Both the lack of knowledge about the gene role under physiological conditions and the emerging link of SBSN to various human diseases, including cancer, attract research interest. The association of SBSN expression with poor prognosis of patients suffering from oesophageal carcinoma, glioblastoma multiforme, and myelodysplastic syndromes suggests that SBSN may play a role in human tumourigenesis. Three SBSN isoforms code for the secreted proteins with putative function as signalling molecules, yet with poorly described effects. In this first review about SBSN, we summarised the current knowledge accumulated since its original description, and we discuss the potential mechanisms and roles of SBSN in both physiology and pathology.

• Klíčová slova
• MAPK signalling, cancer resistance, cancer stem-like cells, immunity, interferon, suprabasin,
• MeSH
• diferenciační antigeny * genetika   metabolismus   MeSH
• karcinogeneze * genetika   metabolismus   MeSH
• lidé MeSH
• nádorové proteiny * genetika   metabolismus   MeSH
• nádory * genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• diferenciační antigeny * MeSH
• nádorové proteiny * MeSH
• SBSN protein, human MeSH Prohlížeč