| 2001 |
Human LSM4 contains symmetrically dimethylated arginine (sDMA) residues in vivo, as determined by mass spectrometry and protein sequencing. This symmetrical dimethylation is required for binding of LSM4 to the Tudor domain of the SMN protein; inhibition of dimethylation by S-adenosylhomocysteine abolished LSM4-SMN Tudor interaction. The PRMT responsible is cytoplasmic. |
Mass spectrometry, protein sequencing, in vitro methylation assay with HeLa cytosolic and nuclear extracts, synthetic peptide competition assay |
RNA (New York, N.Y.) |
High |
11720283
|
| 2016 |
The C-terminal RGG domain of human LSM4 promotes Processing Body (PB) accumulation in human cells. Symmetric dimethylation of arginines within the RGG domain by PRMT5 stimulates PB formation. An RGG-deleted LSM4 mutant failed to rescue PB formation in cells depleted of endogenous LSM4, although it retained the ability to assemble into the Lsm1-7 complex, associate with decapping factors, and promote mRNA decay and translational repression. The HAT1-RBBP7 acetyltransferase complex was identified as an interaction partner of the Lsm4 RGG domain, but no role for this complex in PB metabolism was found. |
RNAi depletion of endogenous LSM4 with re-expression of deletion mutants, PRMT5 depletion, Co-immunoprecipitation, mRNA decay and translational repression assays, fluorescence microscopy of PBs |
Molecular and cellular biology |
High |
27247266
|
| 2013 |
The C-terminal extension of Lsm4 (beyond the Sm domain) directly interacts with both SLBP and 3'hExo on the histone mRNP. Mutations in the C-terminal tail of Lsm4 that prevent SLBP and 3'hExo binding reduce the rate of histone mRNA degradation when DNA synthesis is inhibited. |
Direct binding assays (pulldown/co-immunoprecipitation), site-directed mutagenesis of C-terminal tail, histone mRNA decay assays in mammalian cells |
RNA (New York, N.Y.) |
High |
24255165
|
| 2012 |
Crystal structures of S. pombe Lsm4 (and Lsm3, Lsm5/6/7) were solved, revealing a conserved Sm fold. In the crystal lattice Lsm4 forms a trimer; analytical ultracentrifugation showed Lsm4 undergoes a dynamic equilibrium between monomer and trimer in solution. No RNA binding was detected for Lsm4 alone in RNA binding assays with oligo(U). |
X-ray crystallography, analytical ultracentrifugation, RNA binding assays |
PloS one |
High |
22615807
|
| 2005 |
ICln (a multifunctional protein involved in cell volume regulation and RNA splicing) interacts with LSM4 via its PH domain-like fold, suggesting the ICln PH domain serves as a protein-protein interaction platform linking membrane physiology and RNA processing. |
Protein interaction assay (pulldown/binding assay) with truncated ICln159 mutant and LSM4; structural determination of ICln159 by NMR/crystallography |
The Journal of biological chemistry |
Medium |
15905169
|
| 2008 |
In isotonic conditions, LSM4 associates with the plasma membrane and with ICln (shown by FRET and biochemistry). Hypotonic cell swelling causes dissociation of LSM4 from both the plasma membrane and from ICln. Overexpression of LSM4 inhibits activation kinetics and current density of the swelling-dependent anion channel IClswell, establishing LSM4 as a co-factor in regulatory volume decrease in NIH3T3 and HEK293 cells. |
FRET, biochemical fractionation, electrophysiology, overexpression of LSM4 |
Cellular physiology and biochemistry |
Medium |
19088440
|
| 2000 |
Disruption of the mLsm4 gene in mice causes peri-implantation lethality: null blastocysts implant but die shortly thereafter, establishing that Lsm4 is an essential gene in mammals. The early lethality indicates its role in splicing cannot be compensated by other Lsm proteins. |
Promoter trap gene targeting in murine ES cells, homozygous knockout mouse analysis |
Molecular and cellular biology |
High |
10629062
|
| 2001 |
In K. lactis and S. cerevisiae, the N-terminal 72 amino acids of KlLsm4p containing the Sm-like domains are sufficient to restore cell viability in cells lacking the wild-type protein, but deletion of the carboxy-terminal region results in loss of viability in stationary phase. |
Complementation assay in K. lactis and S. cerevisiae lsm4 deletion mutants with truncated KlLsm4 constructs |
Yeast (Chichester, England) |
Medium |
11561292
|
| 2016 |
In S. cerevisiae, combined deletion of EDC3 and the Q/N-rich C-terminal domain of Lsm4 (edc3Δ lsm4ΔC double mutant) reduces mRNA stability and increases dependence on Ccr4-mediated deadenylation and decapping. The decapping enzyme catalytic subunit Dcp2 accumulates in the nucleus in this double mutant. |
Genetic double mutant analysis in yeast, mRNA stability measurements, epistasis with mRNA decay pathway components, localization of Dcp2 |
Biology open |
Medium |
27543059
|
| 2013 |
Overexpression of the Q/N-rich region of yeast Lsm4 eliminates the prions [PSI+], [URE3], and [RNQ+]. Lsm4 forms an amyloid in vivo, and fluorescence correlation spectroscopy showed that during Lsm4-driven [PSI+] elimination, [PSI+] aggregates increase in size before forming foci in mother cells. |
Overexpression of Lsm4 and subcloning of Q/N-rich region in S. cerevisiae, fluorescence correlation spectroscopy, amyloid detection in vivo |
MicrobiologyOpen |
Medium |
23512891
|
| 2023 |
Purified full-length human LSM4 protein undergoes concentration-dependent liquid-liquid phase separation (LLPS) in vitro. The C-terminus of LSM4 contains a low-complexity domain predicted to drive LLPS. High salt concentrations and 1,6-hexanediol block LSM4-induced LLPS, and fusion of LSM4 droplets is observed in vitro. |
In vitro purification from E. coli, wide-field fluorescence microscopy, 1,6-hexanediol and salt sensitivity assays, bioinformatic disorder prediction |
Molekuliarnaia biologiia |
Medium |
36976747
|
| 2025 |
tRF-31 (a tRNA-derived small RNA) binds directly to LSM4 under normoxic conditions. Under hypoxia, reduced tRF-31 leads to decreased ubiquitination of LSM4, enhancing its protein stability. Stabilized LSM4 translocates to the nucleus and promotes splicing of EDN1 pre-mRNA, driving proliferation of pulmonary artery endothelial cells. |
Binding assay (tRF-31–LSM4 interaction), ubiquitination assay, nuclear fractionation, RNA splicing analysis, overexpression and knockdown in PAECs |
European journal of pharmacology |
Medium |
41354297
|
| 2024 |
SF3B4 physically interacts with LSM4 (shown by Co-IP), and SF3B4 knockdown-mediated inhibition of NSCLC cell functions is rescued by LSM4 overexpression, placing LSM4 downstream of SF3B4 in a pathway promoting lung cancer cell growth, metastasis, and stemness. |
Co-immunoprecipitation (Co-IP), RIP, MeRIP, cell functional rescue assays, xenograft mouse models |
Thoracic cancer |
Low |
38462740
|