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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...

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...

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...

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...

Nonsense-mediated mRNA Decay

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...

Nonsense-mediated mRNA Decay

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...

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Related Experiment Video

Updated: May 22, 2026

Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts

Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts

Published on: May 11, 2018

Enhanced splicing modulation by NMA-modified antisense oligonucleotides.

Karen Ling¹, Thazha P Prakash¹, Jinghua Yu¹

¹Ionis Pharmaceuticals Inc., 2855 Gazelle Ct., Carlsbad, CA 92010, United States.

Nucleic Acids Research

|May 21, 2026

Summary

This summary is machine-generated.

A novel chemical modification for splice-switching antisense oligonucleotides (SSOs), NMA, significantly enhances their potency and duration. This next-generation therapy shows promise for treating genetic diseases like spinal muscular atrophy and Dravet syndrome.

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A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

Published on: September 15, 2021

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Last Updated: May 22, 2026

Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts

Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts

Published on: May 11, 2018

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

Published on: September 15, 2021

Area of Science:

Molecular Biology
Genetics
Drug Discovery

Background:

Aberrant RNA splicing is implicated in numerous human diseases.
Splice-switching antisense oligonucleotides (SSOs) offer a therapeutic strategy to correct splicing defects.
Nusinersen, an SSO with 2'-O-methoxyethyl (MOE) modification, is effective for spinal muscular atrophy.

Purpose of the Study:

To evaluate a next-generation ribose modification, 2'-O-[2-(methylamino)-2-oxoethyl] (NMA), for enhancing SSO properties.
To assess the therapeutic potential of NMA-modified SSOs for genetic disorders.

Main Methods:

Development and characterization of NMA-modified SSOs.
In vivo efficacy studies in human SMN2 transgenic mice.
Evaluation of NMA-SSO activity in modulating SCN1A exon 20N splicing.

Main Results:

A long-lasting NMA-modified SSO, salanersen, demonstrated 3-4 fold higher potency than nusinersen in mice.
NMA-modified SSOs showed 3.5-fold greater potency compared to MOE-modified STK-001 for SCN1A splicing modulation.

Conclusions:

NMA chemistry represents a broadly applicable ribose modification that significantly improves SSO pharmacological profiles.
NMA-modified SSOs are a promising next-generation platform for developing splicing modulation therapies for various genetic diseases.