Regulation of histone H4 Lys16 acetylation by predicted alternative secondary structures in roX noncoding RNAs.
Despite differences in size and sequence, the two noncoding roX1 and roX2 RNAs are functionally redundant for dosage compensation of the Drosophila melanogaster male X chromosome. Consistent with functional conservation, we found that roX RNAs of distant Drosophila species could complement D. melanogaster roX mutants despite low homology. Deletion of a conserved predicted stem-loop structure in roX2, containing a short GUb (GUUNUACG box) in its 3' stem, resulted in a defect in histone H4K16 acetylation on the X chromosome in spite of apparently normal localization of the MSL complex. Two copies of the GUb sequence, newly termed the "roX box," were functionally redundant in roX2, as mutants in a single roX box had no phenotype, but double mutants showed reduced H4K16 acetylation. Interestingly, mutation of two of three roX boxes in the 3' end of roX1 RNA also reduced H4K16 acetylation. Finally, fusion of roX1 sequences containing a roX box restored function to a roX2 deletion RNA lacking its cognate roX box. These results support a model in which the functional redundancy between roX1 and roX2 RNAs is based, at least in part, on short GUUNUACG sequences that regulate the activity of the MSL complex.
Department of Cell Biology and Molecular Medicine, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
Seung-Won
SW
Park
Mitzi I
MI
Kuroda
Yongkyu
Y
Park
D000107:Acetylation; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D016384:Consensus Sequence; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics; D022661:RNA, Untranslated / Q000737:chemistry* / Q000235:genetics; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D014960:X Chromosome / Q000378:metabolism
D006657:Histones; D009692:Nucleic Acid Heteroduplexes; D022661:RNA, Untranslated; D008239:Lysine