A MILI independent piRNA biogenesis pathway residually loads MIWI2 empowering partial germline reprogramming activity.. A MILI independent piRNA biogenesis pathway residually loads MIWI2 empowering partial germline reprogramming activity.

In mice, the PIWI-piRNA pathway is essential to re-establish transposon silencing during male germline reprogramming. The cytoplasmic PIWI protein MILI mediates piRNA-guided transposon RNA cleavage as well as piRNA amplification. MIWI2-bound piRNAs and its nuclear localization are proposed to be dependent upon MILI function. Here, we demonstrate the existence of a piRNA biogenesis pathway that in the absence of MILI that sustains partial MIWI2 function and reprogramming activity.