Disease relevance of LOS1

• The LOS1 open reading frame was tagged with the influenza virus hemagglutinin epitope recognized by the 12CA5 antibody [1].

High impact information on LOS1

• Interestingly, various proteins involved in nuclear-cytoplasmic traffic, such as exportins Cse1p, Mex67p, and Los1p, exhibit a robust BA [2].
• Cex1p co-purifies with the nuclear tRNA export receptors Los1p and Msn5p, the eukaryotic elongation factor eEF-1A, which delivers aminoacylated tRNAs to the ribosome, and the RanGTPase Gsp1p, but not with Cca1p, a tRNA maturation enzyme that facilitates translocation of non-aminoacylated tRNAs across the nuclear pore complex [3].
• Los1p was shown previously to be required for efficient pre-tRNA splicing; we report here that Los1p localizes to the nuclear pores and is linked functionally to several components of the tRNA biogenesis machinery including Pus1p and Tfc4p [4].
• Arc1p was found in a screen for components that interact genetically with Los1p, a nuclear pore-associated yeast protein involved in tRNA biogenesis [5].
• The Ran-GTP-binding exportin, Los1p/Xpo-t, and additional pathway(s) mediate tRNA transport to the cytoplasm [6].

Biological context of LOS1

• Because LOS1 is unessential in yeast, other pathways for tRNA nuclear export must exist [7].
• Disruption or deletion of most of the LOS1 gene was not lethal; cells carrying the disrupted los1 alleles were viable and had phenotypes similar to those of cells carrying the los1-1 allele [8].
• Integration of plasmid DNA at the LOS1 locus confirmed that these clones contained authentic LOS1 sequences [8].
• The 12CA5 antibody recognizes an epitope-tagged protein of the size predicted by the LOS1 open reading frame [1].
• Furthermore, overexpression of full-length or N-terminally truncated Los1p was shown to have dominant-negative effects on cell growth and different nuclear export pathways [9].

Anatomical context of LOS1

• We propose that LOS1 mutations may affect pre-tRNA processing via alteration of the nuclear matrix [1].
• Los1p, the Saccharomyces cerevisiae exportin-t homologue, binds tRNA and functions in pre-tRNA splicing and export of mature tRNA from the nucleus to the cytosol [7].

Associations of LOS1 with chemical compounds

• Los1p cannot be extracted from nuclei by treatment with nucleases, salts, or Triton X-100 [1].

Physical interactions of LOS1

• In a two-hybrid screen, we identified Nup2p as a nucleoporin interacting with Los1p [9].

Regulatory relationships of LOS1

• Thus, LOS1 appears to positively regulate SOL1 [10].

Other interactions of LOS1

• Because LOS1 is nonessential, tRNA export in vertebrate and yeast cells likely involves factors in addition to exportin-t. Mutation of RNA1, which encodes RanGAP, causes nuclear accumulation of tRNAs and poly(A) RNA [11].
• Overproduced PUS4 appears to impede 5'-end processing or export of certain tRNAs in the nucleus in a manner remedied by increased expression of RNase P or LOS1, respectively [12].
• SOL1, the founding member of the S. cerevisiae SOL family, was previously identified as a multi-copy suppressor of the los1 defect in tRNA-mediated nonsense suppression [13].
• However, Sol4p does not act as a los1 multi-copy suppressor [13].
• Saccharomyces cerevisiae Los1p, which is genetically linked to the nuclear pore protein Nsp1p and several tRNA biogenesis factors, was recently grouped into the family of importin/karyopherin-beta-like proteins on the basis of its sequence similarity [9].

Analytical, diagnostic and therapeutic context of LOS1

• Using fluorescence in situ hybridization, we could show that the export of some intronless tRNA species is not detectably affected by the disruption of LOS1 [14].
• Using this antibody for indirect immunofluorescence and cell fractionation studies we show that the LOS1 protein is located in nuclei [1].

References