Disease relevance of SLU7

• We show that SLU7 is an essential gene that contains a small motif with striking similarity to the cysteine-rich zinc knuckle of retroviral nucleocapsid proteins, which has been implicated in RNA binding [1].

High impact information on SLU7

• This suggests that SLU7 is involved in the process of 3' splice site choice, whereas SLU4 fulfills a generic requirement for the second step [1].
• Recently, the human homologs of Prp18 and Slu7 were identified [2].
• SLU7 and a novel activity, SSF1, act during the PRP16-dependent step of yeast pre-mRNA splicing [3].
• The structure is consistent with a model in which Prp18 forms a bridge between Slu7 and the U5 small nuclear ribonucleoprotein particles [4].
• These results suggest that the function of Slt11p is regulated by Slu7p in the spliceosome [5].

Biological context of SLU7

• Although SLU7 encodes an essential gene product, we find that a null allele of prp17 is temperature-sensitive for growth and has a partial splicing defect in vitro [6].
• Removal of 199 amino acids from the N-terminus of the 382 amino acid Slu7 protein did not affect cell viability at 25 degrees C. A more extensive N-terminal deletion of 221 amino acids was lethal, as was a C-terminal deletion of 47 amino acids [7].
• Therefore, Prp8p and Slu7p interact with the 3' splice site at the latest stage of splicing prior to the second catalytic step that can currently be defined, and may be at the active site [8].
• Single alanine mutations of zinc knuckle residues Cys122, His130, and Cys135 had no effect on cell growth, but caused Slu7 function during pre-mRNA splicing in vitro to become dependent on Prp18 [9].
• Alanine cluster mutations of 215EIE217 and 221LELY224 abrogated Slu7 binding to Prp18 in a two-hybrid assay and in vitro, and elicited temperature-sensitive growth phenotypes in vivo [9].

Anatomical context of SLU7

• Recruitment of SLU7 to the spliceosome is greatly enhanced by prior addition of PRP16 [10].

Physical interactions of SLU7

• The structure suggests that one face of Prp18 interacts with the splicing factor Slu7, whereas the more evolutionarily conserved amino acids in Prp18 form the opposite face [4].

Other interactions of SLU7

• Deleted versions of Slu7 were also tested for interaction with Prp18 in the two-hybrid system [7].
• Depletion/reconstitution studies coupled with immunoprecipitations suggest that second step factors are recruited to the spliceosome in the following order: Slu7 --> Prp18 --> Prp22 [9].

Analytical, diagnostic and therapeutic context of SLU7

• Physical interaction between Slu7 and Prp18 was demonstrated by using the two-hybrid assay [7].
• Immunoprecipitation of the products of step 1 by anti-SLU7 antibodies demonstrates that SLU7 is a component of the spliceosome [10].
• Yeast pre-mRNA splicing factors SLU7 and PRP16 are required for cleavage of the 3' splice site and exon ligation in vitro [10].

References