What is aberrant splicing?

What is aberrant splicing?

The proteins encoded by these abnormal transcripts are often truncated or missing domains, thereby altering protein function or conferring new functions altogether. Thus, aberrant splicing regulation has genome-wide effects, potentially altering gene expression in many cancer-associated pathways.

What is an example of alternative splicing?

Alternative splicing is a powerful means of controlling gene expression and increasing protein diversity. The best example is the Drosophila Down syndrome cell adhesion molecule (Dscam) gene, which can generate 38,016 isoforms by the alternative splicing of 95 variable exons.

Can RNA seq detection alternative splicing?

A major application of RNA-Seq is to detect differential alternative splicing, i.e., differences in exon splicing patterns among different biological conditions.

What are the types of alternative splicing?

Five main types of alternative splicing events are depicted. (A) Constitutive splicing; (B) mutually exclusive exons; (C) cassette alternative exon; (D) alternative 3′ splice site; (E) alternative 5′ splice site; and (F) intron retention.

What are the components of the spliceosome?

Each spliceosome is composed of five small nuclear RNAs (snRNA) and a range of associated protein factors. When these small RNAs are combined with the protein factors, they make RNA-protein complexes called snRNPs (small nuclear ribonucleoproteins, pronounced “snurps”).

What is aberrant RNA?

Aberrant RNA splicing/mis-splicing in cancer cells could either confer cell survival and growth advantages through altered cell signaling or cell lineage switch or alternatively cause cell death due to mutations of core spliceosome genes or treatment of small molecule inhibitors (e.g. H3B-8800).

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.

How do you detect alternative splicing?

Quantification of alternative splicing to detect the abundance of differentially spliced isoforms of a gene in total RNA can be accomplished via RT-PCR using both quantitative real-time and semi-quantitative PCR methods.

What is control splicing?

Pre-mRNA splicing is regulated by dynamic phosphorylation/dephosphorylation cycle of SR proteins, which is also an important regulator of alternative splicing patterns. The phosphorylation status of SR proteins also influences the intranuclear trafficking of SR proteins between speckles and transcription sites.

What is the function of splicing regulators?

In general, these splicing regulatory elements (SREs) function by recruiting trans-acting splicing factors that activate or suppress splice site recognition or spliceosome assembly by various mechanisms (Matlin et al. 2005; Chasin 2007).

Which is the best tool for splicing variants analysis?

TSVdb presents a well-organized visualization of exon/junction usage and splicing patterns, which enable users to readily and quickly access, analyze, and interpret splicing variants for interesting genes. Users can investigate the isoform expression between tumor subgroups and the association of splicing variant expression with overall survival.

How are alternative splicing variants related to cancer?

Alternative splicing of a gene produces splicing variants, and accumulating evidence has revealed its essential role in cancer-related processes, implying the urgent need to discover tumor-specific isoforms and uncover their potential functions in tumorigenesis.

Which is a consensus splice site in a gene?

They are termed consensus splice site sequences and include donor (5′) and acceptor (3′) splice sites, branch point and polypyrimidine tract sequences, and auxiliary ciselements including splicing silencers and enhancers (Fig. ​(Fig.11). Open in a separate window Fig. 1 The schematic localization of the cisand transsplicing elements.

How is the GC-AG splice site processed?

The noncanonical GC-AG splice site, like the GT-AG splice pair, is processed by major spliceosome complex. The AT-AC splicing motifs, that are present in U-12 type introns, are recognized by functionally relevant U12-dependent spliceosome called minor spliceosome (Parada et al. 2014).

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