Abstract
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 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 role of MAEL HMG-box domain is reminiscent of that of HMGB1 as a sentinel of immunogenic nucleic acids in the innate immune response.
Highlights
Integrity of the germ cell genome is central to sexual reproduction
A prominent role in transposon control belongs to the piRNA pathway that operates through a conserved group of primarily germline-restricted factors, including Piwi proteins, Tudor domain containing proteins, and a large set of accessory proteins required for various aspects of piRNA biogenesis and function [17,18,19,20,21,22]
The predicted structure shows the HMGbox domain on the surface and not encapsulated by the rest of the molecule. It is connected with the MAEL-specific domain (MSD) domain by an approximately 30-residue linker region that appears devoid of any secondary structural elements (Fig. 1A)
Summary
Integrity of the germ cell genome is central to sexual reproduction. Gamete development presents an ideal environment for the selfish propagation of transposable elements (TEs) such as LINE-1 (L1) [1,2,3,4,5]. Retrotransposon expression peaks during a period of genomewide reprogramming of the embryonic germline but is subsequently extinguished in a sex-specific manner [6,7,8,9,10,11]. Retrotransposon dysregulation is associated with an accumulation of DNA damage, meiotic abnormalities, chromosome segregation errors and embryo lethality [12,13,14,15,16]. A prominent role in transposon control belongs to the piRNA pathway that operates through a conserved group of primarily germline-restricted factors, including Piwi proteins, Tudor domain containing proteins, and a large set of accessory proteins required for various aspects of piRNA biogenesis and function [17,18,19,20,21,22].
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