Studies in immortalized human mitotic cells demonstrated that MRN Complex Interacting Protein (MRNIP) plays a critical role in genome stability, replication fork protection, and the detection of DNA double-strand breaks via liquid–liquid phase separation. Our earlier work in mice identified its essential role in meiosis during spermatogenesis, namely, meiotic sex chromosome inactivation, highlighting its critical importance for male fertility. Apart from that, MRNIP is a poorly characterized protein with little to no data-based evidence of its biophysical and biochemical properties.

In this study, we provide experimental evidence confirming that the N-terminal domain is indeed folded and contains a zinc-ribbon motif. We demonstrate that MRNIP binds a Zn2+ ion at this site, which plays a structural role in stabilizing the folded domain. Together with structural similarity observed across species, these findings support the conserved nature of the N-terminal domain of MRNIP. Our experimental data confirms that the C-terminal region is disordered.

Furthermore, we show that both the N- and C-terminal regions exhibit binding specificity for DNA rather than RNA, under low-salt conditions, suggesting low-affinity interactions, whereas no DNA or RNA binding was observed under physiological salt conditions. Our findings provide insight into the biophysical and biochemical properties of MRNIP and offer a foundation for advancing structural and functional studies of MRNIP.