Splicing at the phase-separated nuclear speckle interface: a model
| Autor: | Liao, Susan E, Regev, Oded |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Spliceosome
AcademicSubjects/SCI00010 RNA Splicing Computational biology Plasma protein binding Biology Heterogeneous ribonucleoprotein particle Heterogeneous-Nuclear Ribonucleoproteins 03 medical and health sciences Exon 0302 clinical medicine SR protein RNA Precursors Genetics Humans Survey and Summary Nucleotide Motifs 030304 developmental biology Cell Nucleus 0303 health sciences Base Sequence Models Genetic Intron RNA Exons RNA splicing Spliceosomes RNA Splicing Factors 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Phase-separated membraneless bodies play important roles in nucleic acid biology. While current models for the roles of phase separation largely focus on the compartmentalization of constituent proteins, we reason that other properties of phase separation may play functional roles. Specifically, we propose that interfaces of phase-separated membraneless bodies could have functional roles in spatially organizing biochemical reactions. Here we propose such a model for the nuclear speckle, a membraneless body implicated in RNA splicing. In our model, sequence-dependent RNA positioning along the nuclear speckle interface coordinates RNA splicing. Our model asserts that exons are preferentially sequestered into nuclear speckles through binding by SR proteins, while introns are excluded through binding by nucleoplasmic hnRNP proteins. As a result, splice sites at exon-intron boundaries are preferentially positioned at nuclear speckle interfaces. This positioning exposes splice sites to interface-localized spliceosomes, enabling the subsequent splicing reaction. Our model provides a simple mechanism that seamlessly explains much of the complex logic of splicing. This logic includes experimental results such as the antagonistic duality between splicing factors, the position dependence of splicing sequence motifs, and the collective contribution of many motifs to splicing decisions. Similar functional roles for phase-separated interfaces may exist for other membraneless bodies. |
| Databáze: | OpenAIRE |
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