| 2013 |
Crystal structure of the heptameric Lsm2-8 complex (including Lsm3) bound to the 3' end of U6 snRNA at 2.8 Å resolution revealed the subunit order Lsm3-2-8-4-7-5-6 in a doughnut-shaped assembly. The four 3'-terminal uridines of U6 snRNA are modularly recognized by Lsm3, Lsm2, Lsm8, and Lsm4; uracil base specificity is conferred by a conserved asparagine residue. The 3'-terminal uracil is sandwiched by His36 and Arg69 of Lsm3 via π-π and cation-π interactions, respectively. |
X-ray crystallography at 2.8 Å with associated biochemical assays |
Nature |
High |
24240276
|
| 2013 |
Crystal structure of S. cerevisiae Lsm1-7 at 2.3 Å resolution showed a heptameric ring with subunit order Lsm1-2-3-6-5-7-4. Pat1 recognition by the Lsm1-7 complex is mediated by Lsm2 and Lsm3 (not by the cytoplasm-specific Lsm1 subunit), as revealed by the 3.7 Å structure of Lsm1-7 bound to the C-terminal domain of Pat1. |
X-ray crystallography at 2.3 Å (Lsm1-7) and 3.7 Å (Lsm1-7–Pat1C complex) |
Cell reports |
High |
24139796
|
| 2013 |
Lsm2 and Lsm3 directly bridge the interaction between the Lsm1-7 heptamer and the C-terminus of Pat1 (Pat1C). The crystal structure of the Lsm2-3–Pat1C complex shows three Pat1C molecules surrounding a heptameric ring of Lsm2-3. The Lsm2-3–Pat1C complex and Lsm1-7–Pat1C complex both stimulate mRNA decapping in vitro to a similar extent and exhibit similar RNA-binding preference. Structure-based mutagenesis confirmed the importance of these contacts for decapping activation in vivo. |
X-ray crystallography, in vitro decapping assay, RNA-binding assay, structure-guided mutagenesis, in vivo functional assay |
Cell research |
High |
24247251
|
| 2008 |
Crystal structure of yeast Lsm3 reveals a novel octameric (8-subunit) ring organization of the Sm-fold, distinct from the canonical heptameric arrangement. The homomeric Lsm3 octamer can directly recruit Lsm6, Lsm2, and Lsm5 from yeast lysate, and the C-terminal tail of Lsm3 engages in inter-ring β-sheet interactions via specific protein–protein contacts. |
X-ray crystallography; pull-down from yeast lysate |
Journal of molecular biology |
Medium |
18329667
|
| 2012 |
Crystal structure of S. pombe Lsm3 shows it forms a heptamer within the crystal lattice and in solution (confirmed by analytical ultracentrifugation). RNA-binding assays demonstrated that Lsm2/3 together bind oligo(U) RNA, whereas Lsm3 alone does not bind oligo(U), indicating that the complete Lsm2/3 heterodimer is required for RNA binding. |
X-ray crystallography, analytical ultracentrifugation, RNA-binding assay |
PloS one |
High |
22615807
|
| 2018 |
Structure-guided alanine scanning of S. cerevisiae Lsm2-8 residues at RNA-binding sites and intersubunit interfaces identified Lsm3-R69A as the sole lethal mutation among 39 positions tested, consistent with Arg69 of Lsm3 being essential for binding the 3'-terminal UUU of U6 snRNA. Deletion of LSM3 (lsm3Δ) is lethal but is rescued by overexpression of U6 snRNA or U6 snRNP subunit Prp24, indicating that the only essential function of the Lsm2-8 ring is to support U6 snRNA. |
Systematic alanine-scanning mutagenesis; yeast genetics (deletion rescue by U6 overexpression or Prp24 overexpression); growth assays |
RNA (New York, N.Y.) |
High |
29615482
|
| 2008 |
In C. elegans embryos, LSM-3 (along with LSM-1) is recruited to P-bodies specifically in somatic blastomeres, not germline blastomeres. This recruitment requires the LET-711/Not1 subunit of the CCR4-NOT deadenylase complex and correlates spatially and temporally with the onset of maternal mRNA degradation. |
Live fluorescence imaging; genetic requirement tested by depleting CCR4-NOT subunit LET-711 |
Developmental biology |
Medium |
18692039
|
| 2015 |
In C. elegans, lsm-3 (along with lsm-1) is required for normal development, reproduction, and motility. Under stress conditions, cytoplasmic LSm proteins aggregate into granules in an LSM-1-dependent manner, and lsm-3 is required for processes regulated by the insulin/IGF-1 signaling (IIS) pathway including aging and pathogen resistance. |
RNAi knockdown, loss-of-function mutations, DAF-16::GFP reporter assays, stress phenotype assays |
RNA (New York, N.Y.) |
Medium |
26150554
|
| 2024 |
ChIP-seq in S. cerevisiae revealed that Lsm3 co-occupies chromatin with Mediator subunits Med1/Med15 at 86 genes, of which 73 are intron-containing ribosomal protein genes. During late exponential growth, Mediator transitions from gene promoters to 3'-exon positions overlapping Lsm3 binding sites ~250 bp downstream of the last intron-exon boundary. This transition correlates with reduced mRNA levels and reduced splicing ratios for these genes, indicating that Lsm3 and Mediator cooperate to control growth-regulated transcription and splicing of ribosomal protein genes. |
ChIP-seq (Lsm3, Med1, Med15); RNA-seq; correlation of chromatin occupancy with mRNA levels and splicing ratios |
Nucleic acids research |
Medium |
38613396
|
| 2014 |
Knockdown of LSM3 (as well as LSM5 or LSM7) in human cells lengthens the circadian period, placing LSM3 as a regulator of circadian rhythm via its role in RNA processing (alternative splicing) of core clock genes. |
siRNA knockdown in human cells; circadian period measurement |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
25288739
|