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

Nurul Mohamad,Mikael Bodén

doi:10.1186/1752-0509-4-44

Abstract

BackgroundCajal bodies, nucleoli, PML nuclear bodies, and nuclear speckles are morpohologically distinct intra-nuclear structures that dynamically respond to cellular cues. Such nuclear bodies are hypothesized to play important regulatory roles, e.g. by sequestering and releasing transcription factors in a timely manner. While the nucleolus and nuclear speckles have received more attention experimentally, the PML nuclear body and the Cajal body are still incompletely characterized in terms of their roles and protein complement.ResultsBy 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.ConclusionsThe 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.

Highlights

Cajal bodies, nucleoli, PML nuclear bodies, and nuclear speckles are morpohologically distinct intranuclear structures that dynamically respond to cellular cues
We evaluate the statistical enrichment of Gene Ontology (GO) terms of proteins belonging to the same nuclear body
We investigate the enrichment of two sequence features, essential for nuclear import and nuclear organization

Summary

Introduction

Nucleoli, PML nuclear bodies, and nuclear speckles are morpohologically distinct intranuclear structures that dynamically respond to cellular cues. Such nuclear bodies are hypothesized to play important regulatory roles, e.g. by sequestering and releasing transcription factors in a timely manner. PML nuclear bodies assemble in response to sumoylation (a post translational modification; [1]). They retain and release regulatory proteins in response to cellular stress (e.g. p53; [2]). At a more general level, nuclear pores regulate protein access to the nucleus [4]

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