| 2002 |
Human LSm1-7 proteins colocalize with mRNA-degrading enzymes Dcp1/2 and Xrn1 in discrete cytoplasmic foci (P-bodies); FRET and co-expression studies show hLSm1-7 form a heptameric complex similar to yeast, and complex formation is required for enrichment in these foci. hLSm1 is predominantly cytoplasmic, whereas hLSm8 is not found in the same foci. |
Subcellular localization by immunofluorescence, FRET, co-expression of wild-type and mutant LSm proteins |
RNA (New York, N.Y.) |
High |
12515382
|
| 2013 |
Crystal structure of S. cerevisiae Lsm1-7 at 2.3 Å resolution reveals 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 shows Pat1 is recognized by Lsm2 and Lsm3, not Lsm1. |
X-ray crystallography (2.3 Å and 3.7 Å resolution structures) |
Cell reports |
High |
24139796
|
| 2005 |
Mutations in yeast Lsm1 affecting predicted RNA-binding and inter-subunit interaction residues impair mRNA decay; mutations affecting RNA contact residues do not affect P-body localization; the C-terminal domain of Lsm1 is important for mRNA decay function in addition to the Sm domain. mRNA 3'-end protection requires binding of the Lsm1-7-Pat1 complex to mRNA prior to decapping activation. |
Site-directed mutagenesis, mRNA decay assays, genetic phenotypic analysis in S. cerevisiae |
Genetics |
High |
15716506
|
| 2009 |
The Lsm1-7-Pat1 complex has a strong intrinsic binding preference for oligoadenylated mRNAs over polyadenylated mRNAs, and this preferential binding is crucial for its mRNA decay function; the complex can also recognize U-tracts at the 3' end of RNA to facilitate decapping and 5'-to-3' decay of histone mRNAs in response to oligouridylation. |
In vitro RNA binding assays, genetic analysis, mRNA decay measurements in yeast |
RNA biology |
High |
19279404
|
| 2013 |
Lsm2 and Lsm3 bridge the interaction between the C-terminus of Pat1 and the Lsm1-7 complex; the crystal structure of Lsm2-3-Pat1C shows three Pat1C molecules surrounding a heptameric ring formed by Lsm2-3; the Lsm2-3-Pat1C complex stimulates decapping in vitro similarly to the full Lsm1-7-Pat1C complex; structure-based mutagenesis confirmed the importance of Lsm2-3-Pat1C interactions for decapping activation in vivo. |
X-ray crystallography, in vitro decapping assay, structure-based mutagenesis, in vivo decapping assay |
Cell research |
High |
24247251
|
| 2014 |
Pat1 contributes directly to RNA binding of the Lsm1-7-Pat1 complex; Lsm1-7 complex alone and Pat1 fragments alone have very low RNA binding activity and cannot discriminate oligoadenylated RNA, but reconstitution of the complex restores RNA binding and oligo(A) preference; Pat1 directly contacts RNA in the context of the complex. The middle domain of Pat1 is essential for its interaction with the Lsm1-7 complex in vivo. |
Protein purification, in vitro RNA binding assays, complex reconstitution, genetic interaction studies |
RNA (New York, N.Y.) |
High |
25035297
|
| 2009 |
Decapping by the Lsm1-7-Pat1 complex requires both binding of the complex to the mRNA and facilitation of post-binding events; RNA binding per se is sufficient for 3'-end protection; lsm1 mutants (lsm1-9, lsm1-14) that retain partial RNA binding but block post-binding steps show dominant inhibition of mRNA decay when overproduced, while lsm1-8 (nearly abolishes RNA binding) does not. |
Genetic analysis with multiple lsm1 point mutants, mRNA decay assays, 3'-end protection assays, overexpression dominant-negative analysis in S. cerevisiae |
RNA (New York, N.Y.) |
High |
19643916
|
| 2008 |
lsm1 mutations that abolish preferential binding to oligoadenylated RNA in vitro (while retaining complex integrity and binding to U-tract RNAs) cause a strong mRNA decay defect in vivo, demonstrating that the oligo(A) tail-mediated enhancement of Lsm1p-7p-Pat1p complex–mRNA interaction is crucial for mRNA decay. |
In vitro RNA binding assays with purified mutant complexes, mRNA decay analysis in vivo in S. cerevisiae |
RNA (New York, N.Y.) |
High |
18719247
|
| 2012 |
The C-terminal domain (CTD) of Lsm1, in addition to the Sm domain, is required for normal RNA-binding activity of the Lsm1-7-Pat1 complex; deletion of the CTD (while preserving the Sm domain) severely impairs in vitro RNA binding and causes mRNA decay and 3'-end protection defects in vivo; overexpression of the CTD polypeptide in trans partially suppresses these defects. |
Deletion mutagenesis, 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
|
| 2016 |
Mutagenic analysis of the C-terminal extension of Lsm1 identified specific residues at the very C-terminal end that are functionally important for RNA binding and mRNA decay function of the Lsm1-7-Pat1 complex. |
Site-directed mutagenesis, in vitro RNA binding assays, in vivo mRNA decay assays in yeast |
PloS one |
Medium |
27434131
|
| 2020 |
High-resolution cryo-EM/crystal structures of Lsm1-7 bound to RNA show the complex strongly discriminates against cyclic phosphates and tightly 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 carboxy-terminal region allows the complex to scan along RNA, suggesting a gated mechanism for accessing internal binding sites. |
High-resolution cryo-EM and X-ray crystallography of Lsm complexes bound to RNA, mutagenesis |
RNA (New York, N.Y.) |
High |
32518066
|
| 2010 |
Reconstituted recombinant LSm1-7 complexes directly bind to two distinct RNA target sequences in the BMV genome: a tRNA-like structure at the 3'-UTR and two internal A-rich single-stranded regions; these sequences regulate translation and replication of the BMV genome in vivo. |
In vitro reconstitution of recombinant LSm1-7, RNA binding assays, in vivo viral replication analysis |
RNA (New York, N.Y.) |
High |
20181739
|
| 2015 |
The Lsm1-7-Pat1 complex acts differentially in viral RNA translation versus recruitment to replication: complex integrity is essential for both, but intrinsic RNA-binding ability is only required for translation. The BMV 1a protein interacts with Lsm1-7-Pat1 complex in an RNA-independent manner to mediate viral RNA recruitment to replication complexes. |
Genetic analysis with lsm1 mutant alleles in yeast BMV replication system, co-immunoprecipitation, RNA-binding assays |
RNA (New York, N.Y.) |
High |
26092942
|
| 2011 |
Lsm1 promotes genomic stability by controlling histone mRNA decay in yeast; cells lacking Lsm1 accumulate excess histones, leading to replication-fork instability; reducing histone gene dosage suppresses the replication sensitivity of lsm1Δ cells, placing excess histone accumulation as the causative factor. |
Genetic epistasis (histone gene dosage suppression), mRNA decay assays, DNA damage sensitivity assays in S. cerevisiae |
The EMBO journal |
High |
21487390
|
| 2009 |
In neuronal dendrites, LSm1 associates with intact mRNAs (not degradation intermediates) in a complex containing the cap-binding protein CBP80, suggesting the complex is assembled in the nucleus and transported to dendrites; neuronal LSm1 is partially nuclear and inhibition of mRNA synthesis increases its nuclear localization; LSm1 and CBP80 shift into dendritic spines upon glutamatergic receptor stimulation, indicating these mRNPs contribute to regulated local protein synthesis. |
Immunofluorescence localization, co-immunoprecipitation, live-cell imaging, pharmacological inhibition of transcription |
The Journal of cell biology |
Medium |
19188494
|
| 2015 |
LSm1 binds to the 3' UTR of Dengue virus RNA; LSm1 knockdown by siRNA reduces viral RNA levels and infectious particle production; the LSm1-viral RNA interaction localizes to P-bodies in the cytoplasm. |
RNA pulldown/co-IP, siRNA knockdown, confocal immunofluorescence, RT-qPCR for viral RNA levels |
International journal of molecular medicine |
Medium |
25872476
|
| 2013 |
The P-body protein LSm1 contributes to activation of HCV IRES-driven translation by miR-122 but is not required for miR-122-mediated repressive function at 3' UTR sites, miR-122 cleavage activity, or miR-122 stimulation of HCV replication; LSm1 does not influence RISC recruitment to the HCV 5' UTR, implying it acts downstream of target binding. |
siRNA knockdown of LSm1, HCV IRES reporter assays, replication assays, RISC recruitment assays |
Nucleic acids research |
Medium |
24141094
|
| 2017 |
Pat1b forms a nuclear complex with the Lsm2-8 heptamer that binds U6 snRNA in Cajal bodies; co-IP and immunofluorescence demonstrate Pat1b/Lsm2-8/U6 snRNA/SART3 interactions connecting to tri-snRNP components; this is distinct from the cytoplasmic Pat1b/Lsm1-7 decapping complex, demonstrating dual roles for Pat1b via distinct Lsm complexes. |
Co-immunoprecipitation, immunofluorescence, RNAi, RNA sequencing |
Cell reports |
Medium |
28768202
|
| 2018 |
The Lsm1-7/Pat1 complex preferentially binds stress-activated mRNAs and acts as a translational repressor in addition to its role in mRNA decay; lsm1 mutants show abnormally high association of mRNAs with polysomes under osmotic stress, and 5P-Seq reveals increased ribosome accumulation upstream of start codons, indicating the complex represses translation initiation particularly for highly expressed stress-induced mRNAs. |
MS2 RNA tagging/purification, polysome profiling, 5P-Seq (co-translational decay sequencing), genetic analysis in yeast |
PLoS genetics |
High |
30059503
|
| 2020 |
Pat1 broadens RNA specificity of Lsm1-7 by enhancing binding to A-rich RNAs and increases cooperativity on all oligonucleotides tested; 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 decapping enzyme complexes Dcp1/Dcp2. |
In vitro RNA binding assays with recombinant purified proteins, biochemical multimerization assays, phase separation assays |
RNA (New York, N.Y.) |
High |
32513655
|
| 2011 |
Structure of the LSm657 assembly intermediate at 2.5 Å reveals three monomers forming a hexameric LSm657-657 ring with canonical Sm fold; NMR and pulldown studies show LSm657 can incorporate LSm23 to assemble further toward native LSm1-7 and LSm2-8 rings, identifying LSm657 as a functional assembly intermediate. |
X-ray crystallography (2.5 Å), NMR spectroscopy, pulldown assays |
Journal of molecular biology |
High |
22001694
|
| 2009 |
LSM1 overexpression in yeast inhibits growth primarily by depleting U6 snRNA levels; excess Lsm1 reduces the availability of Lsm2-7 proteins that normally assemble with Lsm8 to form the Lsm2-8 complex that stabilizes U6 snRNA, thereby disrupting pre-mRNA splicing. |
Genetic analysis, U6 snRNA quantification, hypersensitivity assays in S. cerevisiae |
Nucleic acids research |
Medium |
19596813
|
| 2023 |
LSM1-mediated decay of major satellite repeat RNA (MajSat RNA) is required for preferential incorporation of histone variant H3.3 into the male pronucleus; Lsm1 knockdown in mouse zygotes disrupts nonequilibrium histone H3.3 incorporation and asymmetric H3K9me3 modification; accumulated MajSat RNA in Lsm1-depleted oocytes causes abnormal H3.1 incorporation into the male pronucleus; knockdown of MajSat RNA reverses these defects. |
siRNA knockdown of Lsm1 in mouse zygotes, histone ChIP, RNA quantification, rescue experiments by MajSat RNA knockdown |
Nature communications |
High |
36810573
|
| 2015 |
In C. elegans, lsm-1 mutants have impaired Insulin/IGF-1 signaling (IIS); heat stress-induced translocation of the FOXO transcription factor DAF-16 to the nucleus is dependent on lsm-1; lsm-1 mutants show 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. |
Genetic analysis (RNAi and mutants), DAF-16::GFP reporter, RNA-seq, stress assays in C. elegans |
RNA (New York, N.Y.) |
Medium |
26150554
|
| 1997 |
CaSm (LSM1) encodes a 133-amino acid protein containing two Sm motifs; antisense CaSm RNA reduces anchorage-independent growth of pancreatic cancer cells, indicating CaSm expression is necessary for maintenance of the transformed state. |
Antisense RNA expression, soft agar colony formation assay |
Cancer research |
Medium |
9230209
|