Efficient use of a 'dead-end' GA 5' splice site in the human fibroblast growth factor receptor genes.

EMBO J

Nuffield Department of Medicine, John Radcliffe Hospital, Oxford University, Oxford OX3 9DS, UK.

Published: April 2003

We have investigated use of a conserved non-canonical GA 5' splice site present in vertebrate fibroblast growth factor receptor (FGFR) genes. Despite previous studies suggesting that GA at the beginning of an intron is incompatible with splicing, we observe efficient utilization of this splice site for human FGFR1 gene constructs. We show that use of the GA splice site is dependent on both a conventional splice site six nucleotides upstream and sequence elements within the downstream intron. Furthermore, our results are consistent with competition between the tandem 5' splice sites being mediated by U6 snRNP, rather than U1 snRNP. Thus the GA 5' splice site represents an extension of the adjacent conventional 5' splice site, the first natural example of such a composite 5' splice site.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC152907PMC
http://dx.doi.org/10.1093/emboj/cdg163DOI Listing

Publication Analysis

Top Keywords

splice site
32
splice
9
site
8
site human
8
fibroblast growth
8
growth factor
8
factor receptor
8
conventional splice
8
efficient 'dead-end'
4
'dead-end' splice
4

Similar Publications

Circular RNA Formation and Degradation Are Not Directed by Universal Pathways.

Int J Mol Sci

January 2025

Department of Rare Diseases, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.

Circular RNAs (circRNAs) are a class of unique transcripts characterized by a covalently closed loop structure, which differentiates them from conventional linear RNAs. The formation of circRNAs occurs co-transcriptionally and post-transcriptionally through a distinct type of splicing known as back-splicing, which involves the formation of a head-to-tail splice junction between a 5' splice donor and an upstream 3' splice acceptor. This process, along with exon skipping, intron retention, cryptic splice site utilization, and lariat-driven intron processing, results in the generation of three main types of circRNAs (exonic, intronic, and exonic-intronic) and their isoforms.

View Article and Find Full Text PDF

ADAR Therapeutics as a New Tool for Personalized Medicine.

Genes (Basel)

January 2025

Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.

In the field of RNA therapy, innovative approaches based on adenosine deaminases acting on RNA (ADAR)-mediated site-directed RNA editing (SDRE) have been established, providing an exciting opportunity for RNA therapeutics. ADAR1 and ADAR2 enzymes are accountable for the predominant form of RNA editing in humans, which involves the hydrolytic deamination of adenosine (A) to inosine (I). This inosine is subsequently interpreted as guanosine (G) by the translational and splicing machinery because of their structural similarity.

View Article and Find Full Text PDF

The advent of next-generation sequencing (NGS) has revolutionized the analysis of genetic data, enabling rapid identification of pathogenic variants in patients with inborn errors of immunity (IEI). Sometimes, the use of NGS-based technologies is associated with challenges in the evaluation of the clinical significance of novel genetic variants. In silico prediction tools, such as SpliceAI neural network, are often used as a first-tier approach for the primary examination of genetic variants of uncertain clinical significance.

View Article and Find Full Text PDF

The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that mediates the activity of a variety of downstream pathways upon its activation. These pathways regulate various physiological processes within the cell, including growth, survival, proliferation, and motility. Under normal physiological conditions, this allows MET to regulate various development and regenerative processes; however, mutations resulting in aberrant MET activity and the consequent dysregulation of downstream signaling can contribute to cellular pathophysiology.

View Article and Find Full Text PDF

Neurofibromatosis type 1 (NF1) is a complex neurocutaneous disorder caused by pathogenic variants in the gene. Although genotype-phenotype correlation studies are increasing, robust clinically relevant correlations have remained limited. We conducted a retrospective analysis of data obtained from a cohort of 204 Hungarian individuals, with a mean age of 16 years (age range: 1-33 years).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!