Rbmx, an RNA binding protein encoded by a gene on the X chromosome, is ubiquitously expressed in the nucleus and belongs to a small protein family. It is crucial for normal development, contributing to splicing control, transcription, and genome integrity. It is implicated in pathways related to chromatin state maintenance, telomere stability, and replication stress response, with its functions having important implications for understanding chromosome biology, DNA repair, and mammalian development [2].

In myeloid leukemia, loss of Rbmx and its retrogene Rbmxl1 delays leukemia development, leading to changes in chromatin accessibility, chromosomal breaks, and gaps. Rbmx/L1 directly bind to mRNAs, affect transcription of multiple loci including Cbx5, and control Cbx5 locus nascent transcription. Forced Cbx5 expression can rescue the effects of Rbmx/L1 depletion on cell growth and apoptosis, suggesting Rbmx/L1 control leukemia cell survival by regulating chromatin state through Cbx5 [1].

In telomere stability, Rbmx depletion leads to elevated Telomeric repeat-containing RNA (TERRA) levels, enhanced telomere R-loop formation, replication stress, and telomere instability. Rbmx binds to TERRA and the nuclear exosome targeting protein ZCCHC8, promoting TERRA degradation [3].

In genome stability, Rbmx is an ssDNA binding protein that activates ATR on repetitive DNAs. Rbmx depletion leads to defective TopBP1 localization to replication-stressed sites, inadequate ATR activation, replication defects, and genome instability [4].

In summary, Rbmx is essential for multiple biological processes such as chromatin state regulation, telomere stability maintenance, and genome stability during replication. Its study through gene knockout or conditional knockout mouse models has revealed its significant roles in myeloid malignancies, providing potential therapeutic targets in these disease areas.