HGNC Approved Gene Symbol: LSM6Cytogenetic location: 4q31.22 Genomic coordinates (GRCh38): 4:146,175,702-146,204,435 (from NCBI)▼ DescriptionSm-like proteins...
HGNC Approved Gene Symbol: LSM6
Cytogenetic location: 4q31.22 Genomic coordinates (GRCh38): 4:146,175,702-146,204,435 (from NCBI)
Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; 601061). Sm-like proteins contain the Sm sequence motif, which consists of 2 regions separated by a linker of variable length that folds as a loop. The Sm-like proteins are thought to form a stable heteromer present in tri-snRNP particles, which are important for pre-mRNA splicing.
▼ Cloning and Expression
In a search for human Sm-like proteins, Achsel et al. (1999) fractionated proteins present in purified (U4/U6.U5) tri-snRNPs and isolated 7 Sm-like proteins, which they named LSm2-LSm8. Using partial peptide sequence for database searches, they identified and sequenced EST clones. Using additional sequence obtained by PCR amplification of a HeLa cDNA library, they assembled full-length cDNA sequences for LSM2-LSM8.
Salgado-Garrido et al. (1999) searched database sequence for Sm proteins and identified 16 potential Sm-related genes in yeast as well as some Sm-related genes in human and archaebacteria. Using a multiple sequence alignment of Sm domains, they built a phylogenetic tree of yeast, human, and archaeal Sm and Sm-like proteins.
▼ Gene Function
Using electron-microscopy, Achsel et al. (1999) observed that purified LSm proteins form a heteromer that is stable even in the absence of RNA and exhibits a doughnut-shaped structure similar to the Sm core RNP structure. They demonstrated that the purified LSm heteromer binds specifically to the U6 snRNA at its 3-prime-terminal U-tract. They also showed that the LSm proteins facilitate the formation of U4/U6 RNA duplexes in vitro and concluded that the LSm proteins may play a role in U4/U6 snRNP formation.
Using immunoprecipitation experiments, Salgado-Garrido et al. (1999) concluded that there is a complex of 7 Sm-like proteins bound to RNA in yeast. Lsm2-Lsm8 coprecipitate the U4, U5 and U6 snRNAs and directly associate with the U6 snRNA present in the free U6 snRNP. Additionally, the yeast Lsm2-Lsm7 proteins were found to be associated with the pre-RNase P RNA but not the mature RNase RNA. Using immunoprecipitation experiments from human cell extracts, Salgado-Garrido et al. (1999) showed that the LSM3 and LSM4 proteins are specifically associated with snRNP complexes containing the U6 snRNA. Salgado-Garrido et al. (1999) concluded that Sm and Sm-like proteins assemble in at least 2 functionally conserved complexes of deep evolutionary origin.
By disrupting the Sm and Sm-like genes in yeast, Salgado-Garrido et al. (1999) concluded that disruption of genes encoding Sm-like proteins directly associated with the U6 snRNA (Lsm2-8) generated variable phenotypes. Lsm2, Lsm3, Lsm4, and Lsm8 are essential for vegetative growth. Lsm5, Lsm6, and Lsm7 are not essential for growth; however, their disruptions lead to slow growth especially at elevated temperature. The levels of the U6 snRNA were strongly reduced in the strains harboring the Lsm5, Lsm6, and Lsm7 disruptions. Lsm1 and Lsm9 are dispensable for vegetative growth, but Lsm1 is required for optimal vegetative growth at 30 degrees and is temperature sensitive.
Ingelfinger et al. (2002) determined that human LSM1 to LSM7, but not LSM8, were expressed in HeLa cells within cytoplasmic foci. The foci also contained a decapping enzyme (DCP1/2) and the exonuclease XRN1 (607994). Coexpression of wildtype and mutant LSM proteins, as well as fluorescence resonance energy transfer, indicated that the LSM proteins form a complex similar to one found in yeast. Ingelfinger et al. (2002) concluded that the foci contain a partially or fully assembled machinery for the degradation of mRNA.
Using a library of endoribonuclease-prepared short interfering RNAs (esiRNAs), Kittler et al. (2004) identified 37 genes required for cell division, one of which was LSM6. These 37 genes included several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown.
The International Radiation Hybrid Mapping Consortium mapped the LSM6 gene to chromosome 4 (stSG50602).