Research HighlightPublished: 03 April 2026Genome organizationEytan Zlotorynski1 Nature Reviews Molecular Cell Biology (2026)Cite this articleSubjectsRNA splicingNuclear specklesThe transcriptionally active compartment of mammalian and avian genomes is organized into two main sub-compartments: one that contains many short GC-rich genes, and another with fewer, long genes with lower GC content. The functional implications of this organization, which is less common in other vertebrates and absent in invertebrates, is unclear. In close proximity to the gene-dense GC-rich sub-compartment are condensates known as nuclear speckles, which are formed by two unstructured proteins, SON and SRRM2. Speckles are involved in gene expression, most notably in splicing, but their exact roles are unclear. The work by Małszycki, Martina et al. reveals the origin and role of speckles in splicing.Speckles are thought to concentrate splicing-related RNA-binding proteins, most notably SR proteins, around short GC-rich genes. The authors found most SR proteins to be enriched in speckle-proximal exons in wild-type cells, but not in ΔSpeckles cells. Importantly, a notable increase in exon skipping events in transcripts of speckle-proximal genes was observed in ΔSpeckles cells and in SON-depleted cells (ΔSON cells). Compared to all exons, these ‘speckle-dependent exons’ are exceptionally GC-rich and exhibit an architecture of short GC-rich introns flanking GC-rich exons, known as levelled exon–intron architecture. These results indicated that speckles enable accurate processing of levelled architecture mRNAs by efficiently concentrating splicing factors on their exons.This is a preview of subscription content, access via your institutionAccess optionsAccess Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription27,99 € / 30 dayscancel any timeLearn moreSubscribe to this journalReceive 12 print issues and online access269,00 € per yearonly 22,42 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to the full article PDF.39,95 €Prices may be subject to local taxes which are calculated during checkoutReferencesOriginal articleMałszycki, M. et al. Nuclear speckles enable processing of RNA from GC-rich isochores. Cell https://doi.org/10.1016/j.cell.2026.01.011 (2026)Article PubMed Google Scholar Related articleGiudice, J. & Jiang, H. Splicing regulation through biomolecular condensates and membraneless organelles. Nat. Rev. Mol. Cell Biol. 25, 683–700 (2024)Article CAS PubMed PubMed Central Google Scholar Download referencesAuthor informationAuthors and AffiliationsNature Reviews Molecular Cell Biology http://www.nature.com/nrm/Eytan ZlotorynskiAuthorsEytan ZlotorynskiView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Eytan Zlotorynski.Rights and permissionsReprints and permissionsAbout this article