Splicing factor hSlu7 contains a unique functional domain required to retain the protein within the nucleus.
Precursor-mRNA splicing removes the introns and ligates the exons to form a mature mRNA. This process is carried out in a spliceosomal complex containing >150 proteins and five small nuclear ribonucleoproteins. Splicing protein hSlu7 is required for correct selection of the 3' splice site. Here, we identify by bioinformatics and mutational analyses three functional domains of the hSlu7 protein that have distinct roles in its subcellular localization: a nuclear localization signal, a zinc-knuckle motif, and a lysine-rich region. The zinc-knuckle motif is embedded within the nuclear localization signal in a unique functional structure that is not required for hSlu7's entrance into the nucleus but rather to maintain hSlu7 inside it, preventing its shuttle back to the cytoplasm via the chromosomal region maintenance 1 pathway. Thus, the zinc-knuckle motif of hSlu7 determines the cellular localization of the protein through a nucleocytoplasmic-sensitive shuttling balance. Altogether, this indicates that zinc-dependent nucleocytoplasmic shuttling might be the possible molecular basis by which hSlu7 protein levels are regulated within the nucleus.
Shomron
Noam
N
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 69978.
Reznik
Mika
M
Ast
Gil
G
D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism; D019295:Computational Biology; D006801:Humans; D028884:Karyopherins / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D019913:Nuclear Localization Signals / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D017411:Ribonucleoproteins, Small Nuclear / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016335:Zinc Fingers / Q000235:genetics; D000097606:Exportin 1 Protein
D028884:Karyopherins; D019913:Nuclear Localization Signals; D000072260:RNA Splicing Factors; D018160:Receptors, Cytoplasmic and Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D000097606:Exportin 1 Protein; C490656:SLU7 protein, human