Structure insight of ribonuclease J reveals the basis of RNA metabolism in Mycobacterium tuberculosis

RNA degradosome plays key roles in pre-rRNA maturation and mRNA decay, and mediates isoniazid tolerance in Mycobacterium tuberculosis (Mtb). Mtb ribonuclease J (Mtb-RNase J) is one core enzyme of the RNA degradosome, which comprises RNases, RNA helicases, and glycolytic enzymes. However, how Mtb-RNase J functions in RNA metabolism keeps unclear. Here, we solved the crystal structures of Mtb-RNase J and its complex with single-strand RNA (ssRNA). RNA binding induced the comformation change. Mtb-RNase J showed typical beta lactamase activity and exo/endoribonuclease activities. Mn2+ could dramatically enhanced the ribonuclease activity of Mtb-RNase J, which prefers to bind 8-9 nt ssRNA.We unveiled the novel mechanism of Mtb-RNase J to form the active ribonuclease homodimer. Knockout of RNase J dramatically changed the expression levels of 49 genes in the metabolic pathways and morphologies of Mycobacterium smegmatis. Thus, current study explored the structural basis and function of Mtb-RNase J in RNA metabolism.