Nucleic acid metabolism is structurally organized in the nucleus. DNA replication and transcription have been localized to particular nuclear domains. Additional domains have been identified by their morphology or by their composition; for example, by their high concentration of factors involved in RNA splicing. The domain organization of the nucleus is maintained by the nuclear matrix, a nonchromatin nuclear scaffolding that holds most nuclear RNA and organizes chromatin into loops. The nuclear matrix is built on a network of highly branched core filaments that have an average diameter of 10 nm. Many of the intermediates and the regulatory and catalytic factors of nucleic acid metabolism are retained in nuclear matrix preparations, suggesting that nucleic acid synthesis and processing are structure-bound processes in cells. Tissue-specific and malignancy-induced variations in nuclear structure and metabolism may result from altered matrix architecture and composition.