Related Experiment Video

Updated: Jun 19, 2026

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
07:14

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

A mutation in the nuclear speckle and splicing factor SRRM2 is associated with multisystem proteinopathy and causes

Qingyu Shi1, Chloe Lauder1,2, Jolie Marie Miller1

  • 1Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.

RNA (New York, N.Y.)
|June 17, 2026
PubMed

Insights

A novel mutation in the serine/arginine repetitive matrix 2 gene (SRRM2) is linked to multisystem proteinopathy (MSP). This discovery provides new insights into the molecular mechanisms underlying this degenerative disorder.

Area of Science:

  • Genetics
  • Molecular Biology
  • Neurology

Background:

  • Multisystem proteinopathy (MSP) is a complex degenerative disorder affecting multiple organ systems.
  • Identifying genetic risk factors is crucial for understanding MSP pathogenesis.

Purpose of the Study:

  • To identify the genetic cause of dominantly inherited MSP in a specific family.
  • To elucidate the molecular mechanisms by which SRRM2 mutations contribute to MSP.

Main Methods:

  • Genetic analysis to identify mutations co-segregating with MSP.
  • Functional studies in a cell line model with endogenous SRRM2 mutation.
  • Protein-protein interaction assays and transcriptome analysis.

Main Results:

  • A novel mutation in the serine/arginine repetitive matrix 2 gene (SRRM2) was identified and co-segregated with MSP in the affected family.
  • The SRRM2 mutation disrupted protein-protein interactions with ACIN1, a key splicing factor.
  • Widespread differential gene expression was observed, particularly affecting synapse-associated pathways.

Conclusions:

  • SRRM2 is identified as a novel genetic risk factor for multisystem proteinopathy.
  • The SRRM2 mutation contributes to MSP pathology through disruption of RNA splicing and dysregulation of crucial cellular pathways.
Keywords:
RNA splicingdegenerative disordersgene expression regulationmultisystem proteinopathynuclear speckle

More Related Videos

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

Related Concept Videos

Alternative RNA Splicing02:18

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 Splicing01:32

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 Splicing01:32

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...
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Nonsense-mediated mRNA Decay02:27

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,...