# RNA localization to nuclear speckles follows splicing logic

## TL;DR

This paper shows that RNA localization to nuclear speckles is closely linked to splicing processes, even in non-spliced transcripts, suggesting a shared mechanism.

## Contribution

The study reveals a novel connection between RNA localization to nuclear speckles and splicing logic, including the role of exon-like and intron-like features.

## Key findings

- Speckle localization is enhanced by unspliced exon-like or intron-like sequence features.
- Disease-associated single nucleotide variants reduce speckle localization of isolated exons.
- Speckle localization correlates with splicing kinetics and influences exon inclusion or skipping decisions.

## Abstract

Nuclear speckles are membraneless organelles implicated in multiple RNA processing steps. In this work, we systematically characterize the sequence logic determining RNA localization to nuclear speckles. We find extensive similarities between the speckle localization code and the RNA splicing code, even for transcripts that do not undergo splicing. Specifically, speckle localization is enhanced by the presence of unspliced exon-like or intron-like sequence features. We demonstrate that interactions required for early spliceosomal complex assembly contribute to speckle localization. We also show that speckle localization of isolated endogenous exons is reduced by disease-associated single nucleotide variants. Finally, we find that speckle localization strongly correlates with splicing kinetics of splicing-competent constructs and is linked to the decision between exon inclusion and skipping. Together, these results suggest a model in which RNA speckle localization is associated with the formation of the early spliceosomal complex and enhances the efficiency of splicing reactions.

Graphical Abstract