Title

Molecular anatomy of a speckle

UMMS Affiliation

Department of Cell Biology

Publication Date

6-9-2006

Document Type

Article

Subjects

Cell Line; Cell Nucleus; Female; Gene Expression Regulation; Humans; Nuclear Proteins; Protein Structure, Tertiary; RNA Precursors; RNA Splicing; Ribonucleoproteins; Spliceosomes

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

Direct localization of specific genes, RNAs, and proteins has allowed the dissection of individual nuclear speckles in relation to the molecular biology of gene expression. Nuclear speckles (aka SC35 domains) are essentially ubiquitous structures enriched for most pre-mRNA metabolic factors, yet their relationship to gene expression has been poorly understood. Analyses of specific genes and their spliced or mature mRNA strongly support that SC35 domains are hubs of activity, not stores of inert factors detached from gene expression. We propose that SC35 domains are hubs that spatially link expression of specific pre-mRNAs to rapid recycling of copious RNA metabolic complexes, thereby facilitating expression of many highly active genes. In addition to increasing the efficiency of each step, sequential steps in gene expression are structurally integrated at each SC35 domain, consistent with other evidence that the biochemical machineries for transcription, splicing, and mRNA export are coupled. Transcription and splicing are subcompartmentalized at the periphery, with largely spliced mRNA entering the domain prior to export. In addition, new findings presented here begin to illuminate the structural underpinnings of a speckle by defining specific perturbations of phosphorylation that promote disassembly or assembly of an SC35 domain in relation to other components. Results thus far are consistent with the SC35 spliceosome assembly factor as an integral structural component. Conditions that disperse SC35 also disperse poly(A) RNA, whereas the splicing factor ASF/SF2 can be dispersed under conditions in which SC35 or SRm300 remain as intact components of a core domain.

Rights and Permissions

Citation: Anat Rec A Discov Mol Cell Evol Biol. 2006 Jul;288(7):664-75. Link to article on publisher's site

DOI of Published Version

10.1002/ar.a.20336

Related Resources

Link to article in PubMed

Journal/Book/Conference Title

The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology

PubMed ID

16761280