What diseases are caused by alternative splicing?

What diseases are caused by alternative splicing?

Alternative splicing is particularly important in the brain, and mutations in factors connected with splicing regulation cause a range of neurological diseases, from spinal muscular atrophy (SMA) to amyotrophic lateral sclerosis (ALS; also known as motor neuron disease) (both discussed in more detail below).

What is neurodegeneration symptoms?

Some of the more common symptoms of neurodegenerative diseases include:

  • memory loss.
  • forgetfulness.
  • apathy.
  • anxiety.
  • agitation.
  • a loss of inhibition.
  • mood changes.

Why is alternative splicing important in development and disease?

Alternative splicing expands proteome complexity by generating multiple transcript (and protein) isoforms from a single gene. Numerous alternative splicing events occur during cell differentiation and tissue maturation, suggesting that alternative splicing supports proper development.

Can alternative splicing cause mutations?

Changes in alternative splicing can be the cause or consequence of human diseases. There are only a few reports of mutations in core elements of the splicing machinery that result in human diseases.

What is the biological function of alternative splicing?

The overall function of alternative splicing is to increase the diversity of mRNAs expressed from the genome. Alternative splicing changes proteins encoded by mRNAs, which has profound functional effects.

What is the advantage of alternative splicing?

Alternative splicing affords a significant evolutionary advantage by providing a large source of proteomic diversity. Alternative splicing is often regulated at the tissue level, and tissue-specific variants cooperate to modulate protein–protein interaction networks.

What are some neurodegenerative conditions?


  • Alzheimer’s disease.
  • Amyotrophic lateral sclerosis.
  • Friedreich ataxia.
  • Huntington’s disease.
  • Lewy body disease.
  • Parkinson’s disease.
  • Spinal muscular atrophy.

Why do cells employ alternative splicing?

Key Points. Alternative splicing allows individual genes to generate multiple mRNAs. Many of these mRNAs encode functionally distinct protein isoforms, thereby bridging the gap between genome and proteome. Sometimes, the presence or absence of a single regulator is sufficient to determine alternative splicing pathways.

What happens if splicing does not occur?

Description of mRNA Splicing. Transcription and processing (which includes splicing) of the newly made mRNA occurs in the nucleus of the cell. If the introns are not removed, the RNA would be translated into a nonfunctional protein. Splicing occurs in the nucleus before the RNA migrates to the cytoplasm.

Does alternative splicing remove exons?

In alternative splicing, some sequences serve as exons under some conditions and are included in the final mRNA. At other times, however, the alternative-splicing process may exclude the same sequence, treating it as an intron and removing it from the mature mRNA.

What could be a consequence of an alternative splicing event that results in a different 3 UTR in the transcript?

A consequence of the differential temporal behavior of CR-APA versus UTR-APA in T cell activation is that during early activation there will be more APA events affecting the protein isoform produced while during later stages, APA will lead to transcripts that differ in the length of their 3’UTR and therefore the main …

How does splicing contribute to neurodegenerative diseases?

The continuous changes in splicing patterns and a high demand on many cis- and trans- splicing factors contribute to the susceptibility of neuronal tissues to splicing defects. The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function.

Can splice-switching AOS be used to treat neurodegenerative diseases?

Since most neurodegenerative disorders have highly complicated aetiologies and relatively slow pathogenesis where mutations in multiple genes are involved, splice-switching AOs targeting one gene or one mRNA isoform are likely to be applicable to only a certain proportion of patients with these diseases.

How can splicing defects in Parkinson’s disease be corrected?

With the mounting evidence of aberrant splicing in PD pathogenesis, recent studies are utilising AOs to correct causative splicing defects in PD patients. Splice-switching AOs have been designed to induce skipping of LRRK2 exon 2, leading to the generation of a premature stop codon in the transcript.

What are the types of neurodegenerative diseases?

The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function. Several of the most common neurodegenerative diseases involve some form of splicing defect (s), such as Alzheimer’s disease, Parkinson’s disease and spinal muscular atrophy.