Although it is best known as the cell’s DNA container, the cell nucleus also contains non-DNA structures such as nuclear speckles that occupy a substantial portion of its volume. Also known as SC35 domains, interchromatin granule clusters or splicing speckles, speckles are heavily enriched in factors involved in RNA biogenesis, particularly in SR-protein components of the spliceosome. Hence, speckle research has centred on splicing. By investigating intronless mRNAs that localize at speckles, an article by Wang et al. in 2018 questioned the assumption that nuclear speckles are just for splicing.
Using RNA microinjection, the authors found that intronless mRNAs do not require transcription or polyadenylation to be localized at speckles. Instead, they contain cis-regulatory elements that facilitate speckle localization. These speckle-targeting elements are defined by exon splicing element (ESE) sequences — purine-rich sequences known to recruit SR proteins. ESEs were sufficient to direct speckle localization when added to mature β-globin mRNA, which does not normally localize to speckles. Speckle localization also required SR proteins, indicating that intronless mRNAs co-localize with nuclear speckles using ESE RNA elements and their associated SR proteins.