LYAR
Developmental stage
In an ex vivo erythroid culture system, highly expressed from early (preproerythroblasts) to mid (basophilic normoblasts) maturation. Markedly reduced in more mature erythroblasts (at protein level). The decrease in LYAR protein correlates with the rise of beta-globin (HBB) mRNA levels during erythroid cell differentiation.
Domain
The N-terminal zinc-finger domains are required for the appropriate production of 28S rRNA and the formation of pre-60S particles.
Function
Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs (PubMed:24495227). Also acts at the level of transcription regulation. Along with PRMT5, binds the gamma-globin (HBG1/HBG2) promoter and represses its expression (PubMed:25092918). In neuroblastoma cells, may also repress the expression of oxidative stress genes, including CHAC1, HMOX1, SLC7A11, ULBP1 and SNORD41 that encodes a small nucleolar RNA (PubMed:28686580). Preferentially binds to a DNA motif containing 5'-GGTTAT-3' (PubMed:25092918). Negatively regulates the antiviral innate immune response by targeting IRF3 and impairing its DNA-binding activity (PubMed:31413131). In addition, inhibits NF-kappa-B-mediated expression of pro-inflammatory cytokines (PubMed:31413131). Stimulates phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells (By similarity). Prevents nucleolin/NCL self-cleavage, maintaining a normal steady-state level of NCL protein in undifferentiated embryonic stem cells (ESCs), which in turn is essential for ESC self-renewal (By similarity).
Tissue Specificity
Predominantly expressed in testis.
Cellular localization
- Nucleus
- Nucleus
- Nucleolus
- Cytoplasm
- Cell projection
- Cilium
- Photoreceptor outer segment
- Component of pre-ribosomal particles, including pre-40S, pre-60S and pre-90S (PubMed:24495227). Associated with cytoplasmic ribosomes, but not polysomes, as a component of the 60S subunit (PubMed:24990247). In the retina, predominantly expressed in photoreceptor outer segments (By similarity). In the nucleolus, colocalizes with nucleolin/NCL, therefore may reside in the dense fibrillar component (DFC) (By similarity).
Alternative names
PNAS-5, LYAR, Cell growth-regulating nucleolar protein