roX Genes as Non-Coding RNAs

Deletion of one roX gene has no phenotype, but lack of both transcripts causes male-specific lethality with very few male escapers. MSL complex is not properly targeted to the X chromosome in roX1/roX2 double mutant males (Franke and Baker 1999; Meller and Rattner 2002). Unexpectedly, simultaneous overexpression of MSL1 and MSL2 in roX1 roX2 mutant background can induce the assembly of MSL complex on the X chromosome and increase viability of roX1 roX2 mutant males (Oh et al. 2003). Non-coding RNAs are therefore necessary for dosage compensation in a wild-type condition, but overexpression studies show that they are not the only components mediating targeting of the complex.

Dissection of roX function has been complicated by the fact that RNA forms extensive secondary structures. Furthermore, computational secondary structure prediction for large RNAs is still unreliable. Stuckenholz et al. (2003) used a genetic approach to find functional domains in roX1. They generated sequential deletions of roX1, and tested the rescue ability of the constructs in roX1 roX2 double mutant background. Even though roX1 appears to tolerate short deletions (spanning 10% of transcript length), Stuckenholz and colleagues (2003) could identify a stem-loop structure that at least partially accounts for the function of roX1.As a part of the study,they also showed that the frequency of roX1 roX2 escapers depends on the genetic background, and more precisely on the proximal part of the X chromosome. These results imply that there are other unknown factors modifying the function of roX RNAs.

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