Piwi-interacting piRNAs are a major and essential class of small RNAs in the animal germ cells with a prominent role in transposon control.Efficient piRNA biogenesis and function require a cohort of proteins conserved throughout the animal kingdom.Here we studied Maelstrom (MAEL), which is essential for piRNA biogenesis and germ Multi-Tools cell differentiation in flies and mice.MAEL contains a high mobility group (HMG)-box domain and a Maelstrom-specific domain with a presumptive RNase H-fold.
We employed a combination of sequence analyses, structural and biochemical approaches to evaluate and compare nucleic acid binding of mouse MAEL HMG-box to that of canonical HMG-box domain proteins (SRY and HMGB1a).MAEL HMG-box failed to bind double-stranded (ds)DNA but bound to structured RNA.We also identified important roles of a novel cluster of arginine residues in MAEL HMG-box in these interactions.Cumulatively, our results suggest that the MAEL HMG-box domain may contribute to MAEL function in selective processing of retrotransposon RNA into piRNAs.
In this regard, a cellular Rolling Machines role of MAEL HMG-box domain is reminiscent of that of HMGB1 as a sentinel of immunogenic nucleic acids in the innate immune response.