Is exon skipping alternative splicing?

Exon skipping (ES) is reported to be the most common alternative splicing event due to loss of functional domains/sites or shifting of the open reading frame (ORF), leading to a variety of human diseases and considered therapeutic targets.

What is skipped exon splicing?

In molecular biology, exon skipping is a form of RNA splicing used to cause cells to “skip” over faulty or misaligned sections (exons) of genetic code, leading to a truncated but still functional protein despite the genetic mutation.

How do you know if exon is skipping?

Several computational methods have been developed to detect exon-skipping events, such as ASprofile [1], DiffSplice [2], and DSGseq [3]. Notably, all of the abovementioned methods have been proven to be useful in detecting novel motifs and deciphering the logics of alternative splicing [4].

What happens to exons During alternative splicing?

Alternative splicing is a molecular mechanism that modifies pre-mRNA constructs prior to translation. This process can produce a diversity of mRNAs from a single gene by arranging coding sequences (exons) from recently spliced RNA transcripts into different combinations.

What is exon skipping and how does it work?

How does exon skipping work? Exon skipping uses small drugs called antisense oligonucleotides to help cells skip over a specific exon during splicing. This allows cells to join a different set of exons together to produce a protein that is shorter than usual but may have some function.

Is exon skipping effective?

Conclusions. Current available data do not show evidence that exon-skipping drugs are effective in DMD. Despite potential effectiveness when used at a specific dose, significant side effects were reported with drisapersen.

How does exon skipping work?

What regulates alternative splicing?

Splicing is regulated by trans-acting proteins (repressors and activators) and corresponding cis-acting regulatory sites (silencers and enhancers) on the pre-mRNA. However, as part of the complexity of alternative splicing, it is noted that the effects of a splicing factor are frequently position-dependent.

Can exons be spliced out?

Exon skipping or cassette exon: in this case, an exon may be spliced out of the primary transcript or retained. This is the most common mode in mammalian pre-mRNAs. Mutually exclusive exons: One of two exons is retained in mRNAs after splicing, but not both.

How would exon skipping be used to treat a genetic disease?

Exon skipping is one of the more promising therapeutic options for Duchenne Muscular Dystrophy (DMD). The idea is to use antisense oligonucleotides to splice out selected exons from the pre-mRNA, at or next to the mutation site, so as to generate a translatable transcript from the mutant dystrophin gene.