Pre-mRNA splicing and human disease.

By N. Faustino, T. Cooper. Genes & Development, 2003

1,339 citations recorded by the source corpus.

The precision and complexity of intron removal during pre-mRNA splicing still amazes even 26 years after the discovery that the coding information of metazoan genes is interrupted by introns (Berget et al. 1977; Chow et al. 1977). Adding to this amazement is the recent realization that most human genes express more than one mRNA by alternative splicing, a process by which functionally diverse protein isoforms can be expressed according to different regulatory programs. Given that the vast majority of human genes contain introns and that most pre-mRNAs undergo alternative splicing, it is not surprising that disruption of normal splicing patterns can cause or modify human disease. The purpose of this review is to highlight the different mechanisms by which disruption of pre-mRNA splicing play a role in human disease. Several excellent reviews provide detailed information on splicing and the regulation of splicing (Burge et al. 1999; Hastings and Krainer 2001; Black 2003). The potential role of splicing as a modifier of human disease has also recently been reviewed (NissimRafinia and Kerem 2002).

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9cc5f8a18db638566fb315b66c92b1404e1e3c1c

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Citations in the corpus

Function of alternative splicing. (2005, positive): “Missplicing events in disease Since alternative splicing regulates isoform formation and controls numerous cellular functions, it is not surprising that missplicing events can cause or contribute to human diseases (Philips and Cooper, 2000; Faustino and Cooper, 2003).”
Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome (2017, background): “Noncodingmutations,whichaffect gene expression, regulation, or splicing, are estimated to cause ∼15%–30% of human Mendelian disease (Cartegni et al. 2002; Faustino and Cooper 2003; Lim et al. 2011; Lewandowska 2013).”
Variation in alternative splicing across human tissues (2004, background): “cated in several human genetic diseases [12].”
Understanding alternative splicing: towards a cellular code (2005, background): “The importance of accurate splicing is illustrated by the fact that at least 15%, and perhaps as many as 50%, of human genetic diseases arise from mutations either in consensus splice site sequences or in the more variable auxiliary elements known as exon and intron splicing ENHANCERS (ESEs and IS”
Aberrant and Alternative Splicing in Cancer (2004, background): “Alternative splicing has also been found to be associated with various diseases including growth hormone deficiency, Frasier syndrome, Parkinson’s disease, cystic fibrosis, retinitis pigmentosa, spinal muscular atrophy, and myotonic dystrophy (1, 2).”
In silico prediction of splice-altering single nucleotide variants in the human genome (2014, background): “Since pre-mRNA splicing was first discovered in the 1970s (1,2), DNA variations that disrupt normal splicing have been linked to human genetic diseases (3,4,5).”
Dynamic regulation of genome-wide pre-mRNA splicing and stress tolerance by the Sm-like protein LSm5 in Arabidopsis (2014, background): “Accumulating evidence indicates that poor efficiency or defects in splicing can lead to diseases in humans [2,3] and increase sensitivity to abiotic or biotic stresses in plants [4-6].”