U6 snRNA-associated Sm-like protein LSm4 (LSM4)

LSM4 (U6 snRNA-associated Sm-like protein LSm4) is a member of the Sm-like protein family and is highly conserved in eukaryotes. It is an RNA-binding protein that forms part of several heptameric complexes involved in RNA metabolism, most notably the nuclear Lsm2-8 complex (essential for U6 snRNP biogenesis and pre-mRNA splicing) and the cytoplasmic Lsm1-7 complex (central to mRNA decapping and degradation, and processing body formation). The C-terminal region of LSM4 participates directly in histone mRNA degradation by interacting with mRNA binding proteins SLBP and 3′hExo. LSM4 rings assemble mainly via β-sheet and hydrophobic/salt bridge interactions. Dysregulation of LSM4, particularly overexpression, has been linked to enhanced tumorigenicity and poor outcomes in cancers such as ovarian and breast cancer. Although it has important roles in RNA processing and maintenance of RNA integrity, LSM4 is not currently considered a direct therapeutic target nor are there drugs that specifically modulate its activity. The biological consequences of LSM4 dysfunction are mainly due to disrupted RNA metabolism and splicing.

Other names

Glycine-rich proteinGRPYER112WU6 snRNA-associated Sm-like protein LSm4LSM4 homolog, U6 small nuclear RNA and mRNA degradation associatedLSM4 U6 small nuclear RNA and mRNA degradation associatedLSM4 homolog, U6 small nuclear RNA associated

Not applicable (no drugs targeting this molecule; mechanism relates inherently to RNA binding, RNA degradation, and spliceosome assembly, not to pharmacological action)