| 2002 |
Human LSm1-7 proteins colocalize with mRNA-degrading enzymes Dcp1/2 and Xrn1 in distinct cytoplasmic foci (P-bodies); complex formation (hLSm1-7 but not hLSm8) is required for enrichment in these foci, as shown by FRET and co-expression of wild-type and mutant LSm proteins. |
Subcellular localization by immunofluorescence, FRET, co-expression of wild-type and dominant-negative mutants |
RNA (New York, N.Y.) |
High |
12515382
|
| 2013 |
Crystal structure of S. cerevisiae Lsm1-7 at 2.3 Å shows a heptameric ring with Lsm1-2-3-6-5-7-4 topology; the C-terminal extension of Lsm1 plugs the exit site of the central channel and approaches RNA binding pockets. Structure of Lsm1-7 bound to Pat1 C-terminal domain at 3.7 Å reveals that Pat1 is recognized by Lsm2 and Lsm3, not by Lsm1. |
X-ray crystallography (2.3 Å and 3.7 Å resolution structures) |
Cell reports |
High |
24139796
|
| 2013 |
Lsm2 and Lsm3 bridge the interaction between the C-terminus of Pat1 and the Lsm1-7 complex; the Lsm2-3-Pat1C complex stimulates decapping in vitro; crystal structure of Lsm2-3-Pat1C shows three Pat1C molecules surrounding a heptameric Lsm2-3 ring; structure-based mutagenesis confirmed importance of Lsm2-3-Pat1C interactions for decapping activation in vivo. |
X-ray crystallography, in vitro decapping assay, structure-based mutagenesis, in vivo decapping assays |
Cell research |
High |
24247251
|
| 2005 |
Mutations in predicted RNA-binding and inter-subunit interaction residues of Lsm1p impair mRNA decay and 3'-end protection, demonstrating that Lsm1p-7p complex integrity and its ability to interact with mRNA are essential for mRNA decay function; C-terminal domain of Lsm1p (beyond the Sm domain) is also required for mRNA decay; mutations affecting RNA-contact residues do not affect P-body localization of the complex. |
Deletion and point mutagenesis; in vivo mRNA decay assays; northern blotting; P-body localization by fluorescence microscopy |
Genetics |
High |
15716506
|
| 2020 |
High-resolution cryo-EM/X-ray structures of Lsm1-7 bound to RNA reveal that the complex strongly discriminates against 2',3'-cyclic phosphates and binds oligouridylate tracts with terminal purines; Lsm5 uniquely recognizes purine bases; Lsm1-7 loads onto RNA from the 3' end, and removal of the Lsm1 C-terminal region allows the complex to scan along RNA, suggesting a gated mechanism for accessing internal binding sites. |
High-resolution structural determination (four structures), RNA-binding assays, truncation analysis |
RNA (New York, N.Y.) |
High |
32518066
|
| 2008 |
Two lsm1 point mutants produce Lsm1p-7p-Pat1p complexes that retain complex integrity and general RNA-binding properties but fail to preferentially bind oligoadenylated RNA in vitro, and these mutants show strong mRNA decay defects in vivo, demonstrating that oligoadenylate-tail recognition by Lsm1 is crucial for mRNA decay. |
In vitro RNA-binding assays with purified mutant complexes; in vivo mRNA decay assays; northern blotting |
RNA (New York, N.Y.) |
High |
18719247
|
| 2009 |
Lsm1-7-Pat1 complex has strong intrinsic binding preference for oligoadenylated mRNAs over polyadenylated mRNAs; this preferential binding is crucial for deadenylation-dependent decapping in the 5'-to-3' pathway; the complex also recognizes U-tracts at the 3' end of RNA, facilitating decapping of histone mRNAs in response to oligouridylation. |
In vitro RNA binding assays with purified complex; in vivo mRNA decay assays |
RNA biology |
Medium |
19279404
|
| 2009 |
Decapping activation by the Lsm1-7-Pat1 complex requires both mRNA binding AND facilitation of post-binding steps; lsm1-8 mutant is blocked primarily at the RNA-binding step, while lsm1-9 and lsm1-14 mutants are blocked at post-binding steps; mRNA 3'-end protection requires only the binding step. |
Analysis of lsm1 point mutants; in vitro RNA-binding assays with purified complexes; dominant-negative overproduction experiments; in vivo mRNA decay and 3'-end protection assays |
RNA (New York, N.Y.) |
High |
19643916
|
| 2012 |
The C-terminal domain (CTD) of Lsm1, beyond its Sm domain, is required for normal RNA-binding activity of the Lsm1-7-Pat1 complex; CTD deletion severely impairs mRNA decay and 3'-end protection in vivo and RNA binding in vitro; overexpression of the CTD polypeptide in trans partially suppresses these defects. |
CTD deletion mutants; in vitro RNA-binding assays with purified complexes; in vivo mRNA decay and 3'-end protection assays; trans-complementation |
RNA (New York, N.Y.) |
High |
22450758
|
| 2014 |
Pat1 directly contacts RNA in the context of the Lsm1-7-Pat1 complex; Lsm1-7 alone and Pat1 fragments alone have very low RNA binding activity and cannot recognize the oligo(A) tail, but reconstitution of the complex restores both abilities; the middle domain of Pat1 is essential for interaction with the Lsm1-7 complex in vivo. |
Purification of Lsm1-7 from pat1Δ cells; reconstitution of Lsm1-7-Pat1 complex; in vitro RNA-binding assays; co-immunoprecipitation |
RNA (New York, N.Y.) |
High |
25035297
|
| 2020 |
Pat1 broadens RNA specificity of Lsm1-7 by enhancing binding to A-rich RNAs and increases cooperativity; Pat1 promotes multimerization of the Lsm1-7 complex potentiated by RNA binding; Pat1's inherent ability to multimerize drives liquid-liquid phase separation with multivalent Dcp1/Dcp2 decapping enzyme complexes. |
In vitro binding assays with recombinant purified proteins from fission yeast; multimerization assays; phase separation assays |
RNA (New York, N.Y.) |
Medium |
32513655
|
| 2010 |
Reconstituted recombinant LSm1-7 complexes directly bind two distinct RNA sequences in the BMV genome: a tRNA-like structure at the 3'-UTR and two internal A-rich single-stranded regions; these sequences regulate BMV genome translation and replication in vivo. |
In vitro RNA binding assays with recombinant reconstituted LSm1-7; in vivo mutagenesis of BMV RNA regulatory sequences; reporter assays in yeast |
RNA (New York, N.Y.) |
High |
20181739
|
| 2015 |
The Lsm1-7-Pat1 complex integrity is required for both viral RNA translation and recruitment to replication complexes (Brome mosaic virus); however, the intrinsic RNA-binding ability of the complex is only required for translation, not recruitment; the BMV 1a protein interacts with the Lsm1-7-Pat1 complex in an RNA-independent manner. |
Collection of lsm1 mutant alleles; BMV replication system in yeast; co-immunoprecipitation; RNA-binding assays |
RNA (New York, N.Y.) |
Medium |
26092942
|
| 2013 |
LSm1 (P-body protein) contributes to activation of HCV IRES-driven translation by miR-122, but is not required for miR-122 repressive function at 3' UTR sites, cleavage at perfectly complementary sites, or miR-122 stimulation of HCV replication; LSm1 does not influence RISC recruitment to the HCV 5'UTR. |
siRNA knockdown of LSm1; HCV IRES reporter assays; miR-122 functional assays; RISC recruitment assays |
Nucleic acids research |
Medium |
24141094
|
| 2015 |
LSm1 binds directly to the 3' UTR of Dengue virus RNA (demonstrated by two independent methodologies); this interaction occurs at P-bodies in the cytoplasm; LSm1 knockdown reduces viral RNA levels and infectious particle production, establishing LSm1 as a positive regulator of DENV replication. |
RNA immunoprecipitation; RNA pull-down (two independent methods); confocal immunofluorescence; siRNA knockdown with viral RNA quantification |
International journal of molecular medicine |
Medium |
25872476
|
| 2011 |
Lsm1 is required for genomic stability in S. cerevisiae; lsm1Δ cells show defects in recovery from replication-fork stalling and DNA damage sensitivity; the Lsm1-7-Pat1 complex targets histone mRNAs for decay in yeast, and excess histones accumulate in lsm1Δ cells; reduction of histone gene dosage suppresses the replication-fork instability phenotype of lsm1Δ cells, establishing that improper histone stoichiometry (due to failed histone mRNA decay) causes genomic instability. |
Genetic deletion; northern blotting for histone mRNA levels; histone protein quantification; genetic epistasis (histone gene dosage suppression); DNA damage sensitivity assays |
The EMBO journal |
High |
21487390
|
| 2009 |
In neurons, LSm1 is partially nuclear and associates with intact mRNAs together with the nuclear cap-binding protein CBP80, indicating the dendritic LSm1-mRNP complex is assembled in the nucleus; inhibition of mRNA synthesis increases nuclear LSm1 localization; upon stimulation of glutamatergic receptors, both LSm1 and CBP80 shift significantly into dendritic spines, suggesting translational activation of these mRNPs. |
Immunofluorescence co-localization; subcellular fractionation; live cell imaging; RNA immunoprecipitation; pharmacological manipulation of mRNA synthesis and glutamate receptors |
The Journal of cell biology |
Medium |
19188494
|
| 2009 |
LSM1 over-expression in yeast inhibits growth primarily through depletion of U6 snRNA, thereby impairing pre-mRNA splicing; excess Lsm1 reduces availability of Lsm2-7 proteins for assembly with Lsm8 into the nuclear Lsm2-8 complex that stabilizes U6 snRNA; this is supported by hypersensitivity to loss of other U6 snRNA production/function factors. |
Yeast over-expression; U6 snRNA northern blotting; genetic hypersensitivity analysis; splicing assays |
Nucleic acids research |
Medium |
19596813
|
| 2018 |
The Lsm1-7/Pat1 complex binds preferentially to osmostress-induced mRNAs (STL1, GPD1) and acts as a selective translational repressor; lsm1 and pat1 mutants show defective global translation inhibition under osmotic stress, with abnormally high polysome association of mRNAs; 5P-Seq shows increased ribosome accumulation upstream of start codons in lsm1 mutants, particularly for osmostress-induced mRNAs. |
MS2 RNA tagging for mRNA-protein interaction identification; polysome profiling; 5P-Seq (ribosome footprinting); genetic mutant analysis; protein level measurements |
PLoS genetics |
Medium |
30059503
|
| 2011 |
Crystal structure of the LSm5-6-7 (LSm657) assembly intermediate at 2.5 Å reveals a hexameric ring with canonical Sm fold; NMR confirms hexameric assembly in solution; pull-down and NMR experiments show LSm657 can incorporate LSm2-3, identifying LSm657 as a building block on the assembly route toward the LSm1-7 and LSm2-8 complexes. |
X-ray crystallography (2.5 Å); NMR spectroscopy; pull-down assays |
Journal of molecular biology |
High |
22001694
|
| 2016 |
Specific residues at the very C-terminal end of Lsm1 are functionally important for the RNA-binding activity of the Lsm1-7-Pat1 complex and for mRNA decay in vivo; these residues support function by facilitating RNA binding either directly or indirectly. |
Site-directed mutagenesis of Lsm1 C-terminal extension; in vitro RNA-binding assays with purified mutant complexes; in vivo mRNA decay assays |
PloS one |
Medium |
27434131
|
| 2015 |
C. elegans lsm-1 mutants show impaired heat stress-induced nuclear translocation of the FOXO transcription factor DAF-16, heightened sensitivity to thermal stress and starvation, while lsm-1 overexpression has the opposite effect; under stress, cytoplasmic LSm proteins aggregate into granules in an LSM-1-dependent manner; lsm-1 and lsm-3 are required for aging and pathogen resistance regulated by the Insulin/IGF-1 signaling pathway. |
C. elegans genetic mutants and RNAi; DAF-16::GFP reporter for nuclear translocation; stress survival assays; RNA-seq; fluorescence microscopy of granule formation |
RNA (New York, N.Y.) |
Medium |
26150554
|
| 2023 |
LSM1 mediates major satellite repeat RNA (MajSat RNA) decay in mouse zygotes; knockdown of Lsm1 disrupts nonequilibrium pronucleus histone H3.3 incorporation and asymmetric H3K9me3 modification in the male pronucleus; accumulated MajSat RNA in Lsm1-depleted oocytes causes abnormal H3.1 incorporation into the male pronucleus; knockdown of MajSat RNA rescues the anomalous histone incorporation in Lsm1-knockdown zygotes. |
siRNA knockdown; RNA quantification; chromatin immunoprecipitation for histone variants and modifications; immunofluorescence; epistasis by MajSat RNA knockdown rescue |
Nature communications |
High |
36810573
|
| 1997 |
CaSm (LSM1) encodes a 133-amino acid protein containing two Sm motifs; antisense CaSm RNA reduces the transformed phenotype of pancreatic cancer cells (soft agar colony formation), indicating CaSm expression is necessary for maintenance of the transformed state. |
Antisense RNA expression; soft agar colony formation assay |
Cancer research |
Medium |
9230209
|
| 2017 |
Human Pat1b forms a nuclear complex with Lsm2-8 that binds spliceosomal U6 snRNA and connects to SART3 and U4/U6.U5 tri-snRNP components in Cajal bodies; Pat1b depletion causes preferential upregulation of mRNAs normally found in P-bodies (enriched in AU-rich elements) and changes in >180 alternative splicing events. |
Co-immunoprecipitation; immunofluorescence; RNA immunoprecipitation; RNAi knockdown; RNA sequencing |
Cell reports |
Medium |
28768202
|