Structural and Functional Differences in the Long Non-Coding RNA
in Mouse and Human
Long non-coding RNAs regulate various biological processes such as dosage
compensation, imprinting, and chromatin organization. HOTAIR, a paradigm of this
new class of RNAs, is localized within the human HOXC gene
cluster and was shown, in human cells, to regulate HOXD genes
in trans via the recruitment of Polycomb Repressive Complex
2 (PRC2), followed by the trimethylation of lysine 27 of histone H3. We looked
for the presence of Hotair in mice to assess whether this
in trans mechanism was conserved, in particular at the
developmental stages, when Hoxd genes must be tightly
regulated. We show that the cognate mouse Hotair is poorly
conserved in sequence; and its absence, along with the deletion of the
HoxC cluster, has surprisingly little effect in
vivo, neither on the expression pattern or transcription
efficiency, nor on the amount of K27me3 coverage of different
Hoxd target genes. We conclude that Hotair
may have rapidly evolved within mammals and acquired a functional importance in
humans that is not easily revealed in mice. Alternatively, redundant or
compensatory mechanisms may mask its function when studied under physiological
conditions.
Vyšlo v časopise:
Structural and Functional Differences in the Long Non-Coding RNA
in Mouse and Human. PLoS Genet 7(5): e32767. doi:10.1371/journal.pgen.1002071
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002071
Souhrn
Long non-coding RNAs regulate various biological processes such as dosage
compensation, imprinting, and chromatin organization. HOTAIR, a paradigm of this
new class of RNAs, is localized within the human HOXC gene
cluster and was shown, in human cells, to regulate HOXD genes
in trans via the recruitment of Polycomb Repressive Complex
2 (PRC2), followed by the trimethylation of lysine 27 of histone H3. We looked
for the presence of Hotair in mice to assess whether this
in trans mechanism was conserved, in particular at the
developmental stages, when Hoxd genes must be tightly
regulated. We show that the cognate mouse Hotair is poorly
conserved in sequence; and its absence, along with the deletion of the
HoxC cluster, has surprisingly little effect in
vivo, neither on the expression pattern or transcription
efficiency, nor on the amount of K27me3 coverage of different
Hoxd target genes. We conclude that Hotair
may have rapidly evolved within mammals and acquired a functional importance in
humans that is not easily revealed in mice. Alternatively, redundant or
compensatory mechanisms may mask its function when studied under physiological
conditions.
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Genetika Reprodukčná medicínaČlánok vyšiel v časopise
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