Online Mendelian Inheritance in Man (OMIM) (original) (raw)

* 605974

SLU7 HOMOLOG, SPLICING FACTOR; SLU7

HGNC Approved Gene Symbol: SLU7

Cytogenetic location: 5q33.3 Genomic coordinates (GRCh38) : 5:160,401,641-160,419,081 (from NCBI)

TEXT

Description

SLU7 is a splicing factor required for the selection of the correct adenine-guanine (AG) dinucleotide for 3-prime splice site selection in the second step of pre-mRNA splicing (Chua and Reed, 1999).

Cloning and Expression

Introns are removed from nuclear pre-mRNA in 2 transesterification reactions. Splicing takes place in the spliceosome, a dynamic complex of snRNAs and a large number of proteins. The catalytic center for step 1 is established after a series of spliceosomal intermediate complexes form on pre-mRNA in the order E, A, B, and C, with the catalytic reactions occurring in complex C. Splicing factors for step 2, such as PRP18 (604993) and SLU7, bring near and distant 3-prime splice sites into the active site of the spliceosome. By searching EST databases for homologs of yeast Slu7 and by PCR analysis, Chua and Reed (1999) obtained a cDNA encoding human SLU7. The deduced 586-amino acid protein is 204 amino acids longer than yeast Slu7 and is 41% identical to the worm and Arabidopsis proteins. SLU7 contains a zinc knuckle, a motif found in several splicing factors. Western blot analysis showed expression of a 70-kD nuclear protein that associates with the spliceosome relatively late in the assembly process. The association of SLU7 with the spliceosome is coupled to the catalysis of step 1. Depletion of SLU7 resulted in the accumulation of novel intermediate C-type spliceosomal complexes that were blocked before step 2.

Mapping

Stumpf (2021) mapped the SLU7 gene to chromosome 5q33.3 based on an alignment of the SLU7 sequence (GenBank BC002348) with the genomic sequence (GRCh38).

Gene Function

The production of correctly spliced messenger RNA requires 2 catalytic splicing steps. During step 2, exon 1 attacks an AG dinucleotide at the 3-prime splice site. This AG is usually located between 18 and 40 nucleotides downstream from the branch site, and closer AGs are skipped in favor of AGs located more optimally downstream. Chua and Reed (1999) demonstrated that Slu7 is required for selection of the correct AG for 3-prime splice site selection. In the absence of Slu7, use of the correct AG was suppressed and incorrect AGs were activated. Chua and Reed (1999) investigated this loss of fidelity by analyzing spliceosomes assembled in the absence of Slu7. Their study revealed that exon 1 is loosely associated with these spliceosomes. Chua and Reed (1999) concluded that Slu7 is required to hold exon 1 tightly within the spliceosome for attack on a prespecified AG.

Sorek et al. (2002) showed that more than 5% of human alternatively spliced exons are Alu-derived and that most, if not all, Alu-containing exons are alternatively spliced. Lev-Maor et al. (2003) studied the molecular basis and regulation of the process of turning intronic Alus into new exons. They found that there are at least 238,000 antisense Alus located within introns in the human genome, many of which are susceptible to exonization. Which AG is used within the Alu sequence for splice site selection depends upon the concentration of Slu7. Constitutive exonization of Alus had been shown to cause genetic disease, e.g., Alport syndrome (see COL4A3, 120070.0006), Sly syndrome (253220.0010), and OAT deficiency (258870.0023).

REFERENCES

  1. Chua, K., Reed, R.Human step II splicing factor hSlu7 functions in restructuring the spliceosome between the catalytic steps of splicing. Genes Dev. 13: 841-850, 1999. [PubMed: 10197984] [Full Text: https://doi.org/10.1101/gad.13.7.841\]
  2. Chua, K., Reed, R.The RNA splicing factor hSlu7 is required for correct 3-prime splice-site choice. Nature 402: 207-210, 1999. [PubMed: 10647016] [Full Text: https://doi.org/10.1038/46086\]
  3. Lev-Maor, G., Sorek, R., Shomron, N., Ast, G.The birth of an alternatively spliced exon: 3-prime splice-site selection in Alu exons. Science 300: 1288-1291, 2003. [PubMed: 12764196] [Full Text: https://doi.org/10.1126/science.1082588\]
  4. Sorek, R., Ast, G., Graur, D.Alu-containing exons are alternatively spliced. Genome Res. 12: 1060-1067, 2002. [PubMed: 12097342] [Full Text: https://doi.org/10.1101/gr.229302\]
  5. Stumpf, A. M.Personal Communication. Baltimore, Md. 08/13/2021.

Contributors:

Anne M. Stumpf - updated : 08/13/2021
Ada Hamosh - updated : 5/27/2003

Creation Date:

Paul J. Converse : 5/29/2001

Edit History:

alopez : 08/13/2021
alopez : 03/27/2012
terry : 7/30/2003
terry : 7/30/2003
alopez : 5/28/2003
terry : 5/27/2003
mgross : 5/29/2001