Affiliation:
1. Computer Science Department, Courant Institute of Mathematical Sciences, New York University, New York, NY, USA
Abstract
Abstract
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.
Funder
Simons Foundation
Lalor Foundation
Life Sciences Research Foundation
Publisher
Oxford University Press (OUP)
Reference122 articles.
1. Biomolecular condensates: organizers of cellular biochemistry;Banani;Nat. Rev. Mol. Cell Biol.,2017
2. Cajal bodies, nucleoli, and speckles in the Xenopus oocyte nucleus have a low-density, sponge-like structure;Handwerger;Mol. Biol. Cell,2005
3. The nucleolus;Pederson;Cold Spring Harb. Perspect. Biol.,2011
4. Einige Bemerkungen und Fragen über das Keimbläschen (vesicular germinativa);Wagner;Müller's Arch. Anat Physiol Wiss. Med,1835
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