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Alternative RNA Splicing

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

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Updated: Jun 23, 2025

Isolation of Adult Spinal Cord Nuclei for Massively Parallel Single-nucleus RNA Sequencing

Isolation of Adult Spinal Cord Nuclei for Massively Parallel Single-nucleus RNA Sequencing

Published on: October 12, 2018

Reverse engineering neuron type-specific and type-orthogonal splicing-regulatory networks using single-cell

Daniel F Moakley^1,2,3, Melissa Campbell^1,2,3,4, Miquel Anglada-Girotto^1,5

¹Department of Systems Biology, Columbia University, New York, NY 10032, USA.

Biorxiv : the Preprint Server for Biology

|June 25, 2024

Summary

This summary is machine-generated.

Researchers mapped the alternative splicing (AS) regulatory landscape across 133 mouse neuron types. They identified key RNA-binding proteins (RBPs) driving neuronal identity and specific splicing programs, revealing molecular diversity beyond gene expression.

Keywords:

Elavl2 RNA splicing regulation RNA-binding proteins network inference neuronal subtypes

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Single-cell RNA-Seq of Defined Subsets of Retinal Ganglion Cells

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Area of Science:

Neuroscience
Genomics
Molecular Biology

Background:

Alternative splicing (AS) generates diverse gene isoforms crucial for distinct neuron types.
Existing research on RNA-binding proteins (RBPs) and AS is limited to a few neuron types, necessitating comprehensive modeling.

Purpose of the Study:

To create a holistic map of the neuron type-specific AS regulatory landscape.
To identify RBPs and splicing modules that define neuronal identity and diversity.

Main Methods:

Network reverse engineering applied to single-cell transcriptomes from 133 mouse neocortical cell types.
Inferred regulons of 350 RBPs and their cell type-specific activities.
In vitro validation of RBP function using an ESC differentiation system.

Main Results:

Successfully mapped the AS regulatory landscape and inferred 350 RBP regulons with cell type-specific activities.
Identified Elavl2 as a key RBP regulating MGE-specific splicing in GABAergic interneurons.
Discovered exon and regulator modules specific to long- and short-projection neurons across various neuronal classes.

Conclusions:

The study provides a valuable resource for understanding splicing regulatory programs that drive neuronal molecular diversity.
Neuronal identity is shaped by AS regulatory programs, some of which are independent of gene expression classifications.
This work advances the understanding of how alternative splicing contributes to the complexity of the nervous system.