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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.
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Related Experiment Video

Updated: Mar 13, 2026

Use of Alu Element Containing Minigenes to Analyze Circular RNAs

Use of Alu Element Containing Minigenes to Analyze Circular RNAs

Published on: March 10, 2020

Dynamic ASXL1 Exon Skipping and Alternative Circular Splicing in Single Human Cells.

Winston Koh¹, Veronica Gonzalez², Sivaraman Natarajan²

¹Departments of Bioengineering and Applied Physics, Stanford University, Stanford, CA, 94305, United States of America.

|October 14, 2016

Summary

This summary is machine-generated.

This study reveals how circular RNA (circRNA) splicing occurs for ASXL1. Efficient circRNA formation needs specific DNA elements and transcriptional start sites, challenging previous understandings of circRNA biogenesis.

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Area of Science:

Molecular Biology
Genetics
RNA Biology

Background:

Circular RNAs (circRNAs) are a novel class of noncoding RNA with largely unknown functions.
The biogenesis and regulation of circRNAs, particularly ASXL1 circRNAs, remain poorly understood.

Purpose of the Study:

To investigate the mechanisms underlying ASXL1 circular splicing.
To characterize the relationship between linear and circular ASXL1 isoforms within single cells.

Main Methods:

Targeted deletion and high-resolution splicing detection.
Single-cell sequencing and isoform analysis.
Absolute quantification of RNA isoforms.

Main Results:

Efficient ASXL1 circular splicing requires the canonical transcriptional start site and inverted AluSx elements.
ASXL1 overexpression leads to promiscuous linear splicing, with dominant products skipping exons involved in circRNA formation.
Single-cell sequencing shows distinct cellular preferences for either linear or circular ASXL1 isoforms.
Standard methods may overestimate circRNA abundance.

Conclusions:

ASXL1 circRNA biogenesis is a dynamic process influenced by specific sequence elements and transcriptional regulation.
A reciprocal expression relationship exists between certain linear and circular ASXL1 isoforms within individual cells.
This study provides a new framework for understanding circRNA genesis and function.