ITQB publishes 3D Structure of RNase II in Nature

Oeiras, 07/09/06

In this issue of Nature, a paper by ITQB researchers reports the 3D structural determination of the bacterial ribonuclease II, an enzyme that degrades RNA molecules, the messengers of the genome.

This paper results from the collaboration between the Laboratory of Control of Gene Expression (headed by Cecília Arraiano) and the Laboratory of Crystallography (headed by Maria Arménia Carrondo). Two structures were obtained; the structure of the native RNase II and the structure of a mutant RNase II that holds to RNA molecules without degrading them. The comparison between both structures together with the extensive molecular and biochemical data already obtained showed how RNase II kills its target.

The structure of RNase II is organized in four distinct domains. The enzyme establishes contact with the RNA in two distinct regions – the anchor and the catalytic regions – that pull the RNA molecule inside the enzyme by its tail (3´end). Catalysis takes places in a pocket inside the enzyme, which is only accessible to linear single stranded RNA, explaining the specificity for RNA versus DNA cleavage. The structure also elucidates the dynamic mechanism of RNA degradation. The architecture of the catalytic domain now revealed is totally different from other RNases and could not have been determined by simple sequence analysis.

Elucidating the structure of this RNase can now provide additional clues on how cells regulate the fine tuning of gene expression in bacteria but also extrapolate to other RNases of the same family, which are present also in eukaryotes where they regulate important cellular functions.