Argonaute super family proteins comprise AGO and PIWI clades that are generally guided by small RNAs to cleave target transcripts. Although AGO clade proteins are highly efficient to cleave target transcripts, Arif et al. demonstrated that PIWI proteins are sluggish in cleaving their targets, thereby requiring additional factor, GTSF1, which transforms PIWI proteins into efficient endoribonuclease. Arif and her colleagues’ findings provide the first example of an auxiliary protein potentiating the catalytic activity of Argonaute super family protein.

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