Abstract
BackgroundThousands of different long non-coding RNAs are expressed during embryonic development, but the function of these molecules remains largely unexplored.ResultsHere we characterize the expression and function of Six3OS, a long non-coding RNA that is transcribed from the distal promoter region of the gene encoding the homeodomain transcription factor Six3. Overexpression and knockdown analysis of Six3OS reveals that it plays an essential role in regulating retinal cell specification. We further observe that Six3OS regulates Six3 activity in developing retina, but does not do so by modulating Six3 expression. Finally, we show that Six3OS binds directly to Ezh2 and Eya family members, indicating that Six3OS can act as a molecular scaffold to recruit histone modification enzymes to Six3 target genes.ConclusionsOur findings demonstrate a novel mechanism by which promoter-associated long non-coding RNAs can modulate the activity of their associated protein coding genes, and highlight the importance of this diverse class of molecules in the control of neural development.
Highlights
Thousands of different long non-coding RNAs are expressed during embryonic development, but the function of these molecules remains largely unexplored
It has recently become clear that long non-coding RNAs comprise a large fraction of the mammalian transcriptome [1]
Much effort has been focused on functional analysis of long non-coding RNA (lncRNA) that are processed into short fragments, such as microRNAs, that regulate expression of protein coding genes via homologous base pairing
Summary
Thousands of different long non-coding RNAs are expressed during embryonic development, but the function of these molecules remains largely unexplored. It has recently become clear that long non-coding RNAs (lncRNAs) comprise a large fraction of the mammalian transcriptome [1]. Some lncRNAs act via antisense base pairing to block gene expression [5,6,7], but many show no clear sequence overlap with the mRNAs of protein coding genes. Several of these lncRNAs are known instead to
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