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Updated: Jun 5, 2026

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

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Published on: April 26, 2017

High-throughput engineering of ligand-activated splicing ribozyme through domain insertion.

August Staubus¹, Ella Ramamurthy², Anika Gupta²

¹Biochemistry and Cell Biology Graduate Program, Rice University, Houston, TX, USA.

Biorxiv : the Preprint Server for Biology

|June 4, 2026

Summary

Researchers engineered ligand-activated splicing ribozymes (LASRs) from catalytic introns. These RNA-based systems enable ligand-dependent control of gene expression and intracellular chemical signal recording across diverse organisms.

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Area of Science:

Molecular Biology
Synthetic Biology
RNA Engineering

Background:

Protein engineering uses domain insertion for ligand-mediated control.
Systematic application to large, structured RNAs like catalytic introns is not well-established.

Purpose of the Study:

Investigate engineering ligand-activated splicing ribozymes (LASRs) from group I catalytic introns.
Map aptamer insertion sites for ligand-dependent control.
Establish LASRs as a versatile RNA-based control platform.

Main Methods:

Domain-insertion profiling coupled with high-throughput screening.
Nucleotide-resolution landscape mapping of aptamer insertion.
Integration with a genetic recorder for ribosomal RNA information writing.

Main Results:

Identified specific sites for robust ligand-dependent control in ribozymes.
Demonstrated LASR functionality across bacteria and fungi.
Enabled sequencing-based recovery of intracellular chemical signals from microbial consortia.

Conclusions:

LASRs are a feasible RNA-based inducible control platform.
LASRs can sense diverse chemical inputs and regulate gene expression.
LASRs facilitate recording of intracellular information in RNA.