The proteins of intra-nuclear bodies: a data-driven analysis of sequence, interaction and expression

By collating recent experimentally verified data, we find that almost 1000 proteins in the mouse nuclear proteome are known to associate with one or more of the nuclear bodies. Their gene ontology terms highlight their regulatory roles: splicing is confirmed to be a core activity of speckles and PML nuclear bodies house a range of proteins involved in DNA repair. We train support-vector machines to show that nuclear proteins contain discriminative sequence features that can be used to identify their intra-nuclear body associations. Prediction accuracy is highest for nucleoli and nuclear speckles. The trained models are also used to estimate the full protein complement of each nuclear body. Protein interactions are found primarily to link proteins in the nuclear speckles with proteins from other compartments. Cell cycle expression data provide support for increased activity in nucleoli, nuclear speckles and PML nuclear bodies especially during S and G2 phases.The large-scale analysis of the mouse nuclear proteome sheds light on the functional organization of physically embodied intra-nuclear compartments. We observe partial support for the hypothesis that the physical organization of the nucleus mirrors functional modularity. However, we are unable to unambiguously identify proteins' intra-nuclear destination, suggesting that critical drivers behind of intra-nuclear translocation are yet to be identified.The nucleus not only houses the genetic material but also administers its transcription. Morphologically defined intra-nuclear compartments or bodies are non-randomly interspersed amongst chromosomes. Preliminary evidence indicates that these compartments are spatially and functionally organized, and play important regulatory roles. For example, nucleoli are primarily concerned with ribosomal biogenesis at sites of ribosomal genes, nuclear speckles accumulate pre-mRNA splicing factors at actively transcribed genes, and nuclear pore complexes sit in the nuclear membra