LSM4/YER112W Summary Help

Standard Name LSM4 1
Systematic Name YER112W
Alias SDB23 , USS1
Feature Type ORF, Verified
Description Lsm (Like Sm) protein; part of heteroheptameric complexes (Lsm2p-7p and either Lsm1p or 8p): cytoplasmic Lsm1p complex involved in mRNA decay; nuclear Lsm8p complex part of U6 snRNP and possibly involved in processing tRNA, snoRNA, and rRNA; forms cytoplasmic foci upon DNA replication stress (2, 3, 4, 5 and see Summary Paragraph)
Name Description Like SM 1
Chromosomal Location
ChrV:387232 to 387795 | ORF Map | GBrowse
Gene Ontology Annotations All LSM4 GO evidence and references
  View Computational GO annotations for LSM4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 10 genes
Classical genetics
reduction of function
Large-scale survey
reduction of function
304 total interaction(s) for 183 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 84
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 24
  • Biochemical Activity: 1
  • Co-localization: 2
  • Co-purification: 6
  • PCA: 22
  • Protein-RNA: 3
  • Reconstituted Complex: 1
  • Two-hybrid: 56

Genetic Interactions
  • Dosage Rescue: 5
  • Negative Genetic: 72
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 6
  • Positive Genetic: 13
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 1
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 187
Molecular Weight (Da) 21,276
Isoelectric Point (pI) 10.31
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrV:387232 to 387795 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..564 387232..387795 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000914

The Sm and Sm-like (Lsm) proteins are a highly conserved family of ancient origin, found in bacteria, archaea, and eukaryotes. These proteins were first characterized in humans with systemic lupus erythemathosus, where autoantibodies were found that recognize an antigen called Sm. The Sm antigen was characterized as a domain present in a group of eight small proteins (alternatively spliced products B and B', as well as D1, D2, D3, E, F, and G) that associated with four of the five snRNAs (U1, U2, U4, and U5, but not U6) involved in splicing of nuclear pre-mRNAs (6). The S. cerevisiae genome contains 16 proteins containing an Sm, or Sm-like, domain. Seven genes encode proteins corresponding to the human Sm antigen proteins: SMB1 (Sm B), SMD1 (Sm D1), SMD2 (Sm D2), SMD3 (Sm D3), SME1 (Sm E), SMX3 (Sm F), and SMX2 (Sm G). An additional eight genes, LSM1, LSM2, LSM3, LSM4, LSM5, LSM6, LSM7, and LSM8 also encode proteins containing Sm domains and are thus named LSM (Like SM) proteins. These proteins are more closely related to individual Sm proteins than to each other. MAK31 has also been reported to contain an Sm domain (6).

Crystal structures of human Sm proteins, in pairs or with U1 snRNA, indicate that the seven core Sm proteins form a heteroheptameric ring with a small central hole (7, 8, 9). The Sm site, the conserved uridine rich sequence found near the 3-prime ends of the U1, U2, U4, and U5 snRNAs, appears to form contacts along the inner surface of the ring complex and it is suggested that the RNA may pass through the hole (7, 8, 9). Experiments in S. cerevisiae indicate that a similar seven-membered ring containing one copy of each of the seven Sm proteins exists in yeast (10). Similarly to the Sm proteins, the Lsm proteins also form heteroheptameric rings. In S. cerevisiae, as well as in other eukaryotes, two different Lsm ring complexes exist, containing Lsm2p-7p and either Lsm1p or Lsm8p (4).

The Lsm proteins are found in two distinct heteroheptameric complexes. Each complex contains Lsm2p, Lsm3p, Lsm4p, Lsm5p, Lsm6p, Lsm7p, and a seventh protein, either Lsm1p or Lsm8p (11). By analogy with the Sm proteins, it is thought that the Lsm proteins also form a seven-membered ring structure (12).

The complex containing Lsm8p localizes to the nucleus (4), associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP) and by binding directly to the U6 snRNA, plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes and thus in splicing of nuclear mRNAs (1, 6, 11, 4, 12). The Lsm2-8 proteins bind specifically to the 3'-terminal U-tract of the U6 snRNA and facilitate the binding of the splicing factor Prp24p (12, 13). It is also thought that the Lsm2-8 complex plays a role in the degradation of nuclear RNA substrates by targeting them for decapping (3).

The complex containing Lsm1-7p is cytoplasmic and mutations in LSM1-7 all cause defects in mRNA degradation (2). Lsm1-7p are found in association with the Pat1p decapping enzyme and Xrn1p exoribonucleases; thus the Lsm1-7 complex is thought to be involved in mRNA degradation via the decapping step (11, 4, 14).

There may be yet another Lsm complex, containing at least six members (Lsm2-7p), as these six proteins, but not Lsm1p or Lsm8p, have been found in association with the pre-RNase P RNA (4, 6) and with the box H/ACA snoRNA snR5 (15).

Because it has been observed that cells depleted of any of the essential Lsm proteins (Lsm2-5p or Lsm8p), are defective in processing of tRNA (16), rRNA (17), and snoRNA (18), it has been suggested that the Lsm proteins may have the additional role of directly processing these classes of RNAs. However, it has also been observed that these phenotypes are alleviated by overexpression of the U6 snRNA, so it may be that these other RNA processing defects are downstream effects of lowering U6 levels and thus inhibiting splicing (15).

Last updated: 2006-01-26 Contact SGD

References cited on this page View Complete Literature Guide for LSM4
1) Mayes AE, et al.  (1999) Characterization of Sm-like proteins in yeast and their association with U6 snRNA. EMBO J 18(15):4321-31
2) He W and Parker R  (2000) Functions of Lsm proteins in mRNA degradation and splicing. Curr Opin Cell Biol 12(3):346-50
3) Kufel J, et al.  (2004) Nuclear pre-mRNA decapping and 5' degradation in yeast require the Lsm2-8p complex. Mol Cell Biol 24(21):9646-57
4) Beggs JD  (2005) Lsm proteins and RNA processing. Biochem Soc Trans 33(Pt 3):433-8
5) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
6) Salgado-Garrido J, et al.  (1999) Sm and Sm-like proteins assemble in two related complexes of deep evolutionary origin. EMBO J 18(12):3451-62
7) Kambach C, et al.  (1999) Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell 96(3):375-87
8) Stark H, et al.  (2001) Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle. Nature 409(6819):539-42
9) Pomeranz Krummel DA, et al.  (2009) Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution. Nature 458(7237):475-80
10) Walke S, et al.  (2001) Stoichiometry of the Sm proteins in yeast spliceosomal snRNPs supports the heptamer ring model of the core domain. J Mol Biol 308(1):49-58
11) Bouveret E, et al.  (2000) A Sm-like protein complex that participates in mRNA degradation. EMBO J 19(7):1661-71
12) Achsel T, et al.  (1999) A doughnut-shaped heteromer of human Sm-like proteins binds to the 3'-end of U6 snRNA, thereby facilitating U4/U6 duplex formation in vitro. EMBO J 18(20):5789-802
13) Ryan DE, et al.  (2002) The 5' and 3' domains of yeast U6 snRNA: Lsm proteins facilitate binding of Prp24 protein to the U6 telestem region. RNA 8(8):1011-33
14) Tharun S, et al.  (2000) Yeast Sm-like proteins function in mRNA decapping and decay. Nature 404(6777):515-8
15) Fernandez CF, et al.  (2004) An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5. Mol Biol Cell 15(6):2842-52
16) Kufel J, et al.  (2002) Lsm proteins are required for normal processing of pre-tRNAs and their efficient association with La-homologous protein Lhp1p. Mol Cell Biol 22(14):5248-56
17) Kufel J, et al.  (2003) Lsm Proteins are required for normal processing and stability of ribosomal RNAs. J Biol Chem 278(4):2147-56
18) Kufel J, et al.  (2003) A complex pathway for 3' processing of the yeast U3 snoRNA. Nucleic Acids Res 31(23):6788-97