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RNA Splicing

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...

Alternative RNA Splicing

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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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Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
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BRIE2: computational identification of splicing phenotypes from single-cell transcriptomic experiments.

Yuanhua Huang^1,2, Guido Sanguinetti^3,4

¹School of Biomedical Sciences, University of Hong Kong, Hong Kong SAR, Pok Fu Lam, China. yuanhua@hku.hk.

|August 28, 2021

Summary

This summary is machine-generated.

This study introduces BRIE2, a computational tool that links RNA splicing events to cell phenotypes from single-cell RNA sequencing data. BRIE2 helps identify disease-associated splicing and improves RNA velocity analysis.

Keywords:

Differential alternative splicing Differential momentum genes Single-cell RNA-seq Variational Bayes

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Area of Science:

Computational Biology
Genomics
Single-cell analysis

Background:

RNA splicing drives cellular heterogeneity and transcriptional kinetics.
Single-cell RNA sequencing (scRNA-seq) coverage limits hinder linking splicing to cell phenotypes.
Existing methods struggle to associate specific splicing events with cell-level characteristics.

Purpose of the Study:

To develop a scalable computational method for associating RNA splicing with cell phenotypes.
To overcome limitations of scRNA-seq coverage for splicing event analysis.
To improve the understanding of RNA splicing's role in cellular heterogeneity and disease.

Main Methods:

Development of BRIE2, a scalable computational method.
Regression of single-cell transcriptomic data against cell-level features.
Application of BRIE2 to identify differential alternative splicing events and gene selection for transcriptional kinetics.

Main Results:

BRIE2 effectively identifies differential disease-associated alternative splicing events.
BRIE2 enables principled selection of genes capturing transcriptional kinetics heterogeneity.
Improved RNA velocity analyses using BRIE2-selected genes.

Conclusions:

BRIE2 resolves challenges in associating splicing events with cell phenotypes in scRNA-seq data.
The method facilitates the identification of splicing phenotypes linked to biological changes.
BRIE2 enhances the utility of scRNA-seq for studying splicing dynamics and cellular heterogeneity.