The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration

Abstract

The RNA binding protein Larp1 was originally shown to be involved in spermatogenesis, embryogenesis and cell-cycle progression in Drosophila. Our data show that mammalian Larp1 is found in a complex with poly A binding protein and eukaryote initiation factor 4E and is associated with 60S and 80S ribosomal subunits. A reduction in Larp1 expression by siRNA inhibits global protein synthesis rates and results in mitotic arrest and delayed cell migration. Consistent with these data we show that Larp1 protein is present at the leading edge of migrating cells and interacts directly with cytoskeletal components. Taken together, these data suggest a role for Larp1 in facilitating the synthesis of proteins required for cellular remodelling and migration.

Overexpression of a LAM Domain Containing RNA-Binding Protein LARPIc Induces Precocious Leaf Senescence in Arabidopsis

“…In animals, LARP1s are mainly cytoplasmic proteins that function in metabolism of specific mRNAs. LARP1 formed a complex with PABP and eIF4E and was localized to P-bodies, where mRNA decay occurs (Blagden et al, 2009;Burrows et al, 2010;Chauvet et al, 2000;Ichihara et al, 2007;Nykamp et al, 2008;Singh et al, 2011). Furthermore, LARP1 is involved in cellular remodeling, migration, and apoptosis (Burrows et al, 2010).…”

“…LARP1 formed a complex with PABP and eIF4E and was localized to P-bodies, where mRNA decay occurs (Blagden et al, 2009;Burrows et al, 2010;Chauvet et al, 2000;Ichihara et al, 2007;Nykamp et al, 2008;Singh et al, 2011). Furthermore, LARP1 is involved in cellular remodeling, migration, and apoptosis (Burrows et al, 2010). Deletion of LARP1 leads to developmental defects during spermatogenesis in D. melanogaster (Blagden et al, 2009;Ichihara et al, 2007) and oogenesis in C. elegans (Nykamp et al, 2008).…”

“…CeLARP1 is localized in the procession bodies (P-bodies) where mRNA decay occurs, and null-mutant worms accumulated a high level of mRNAs in the Ras-MAPK pathway, indicating that CeLARP1 functions to attenuate specific mRNA levels by promoting mRNA decay (Nykamp et al, 2008). More recently, human LARP1 was shown to form a complex with PABP and the cap-binding protein eukaryote initiation factor 4E (eIF4E) (Burrows et al, 2010). Reduced expression of LARP1 in HeLa cells led to decreased global protein synthesis rates, and resulted in cell cycle arrest and an inhibition of cell migration (Burrows et al, 2010).…”

“…More recently, human LARP1 was shown to form a complex with PABP and the cap-binding protein eukaryote initiation factor 4E (eIF4E) (Burrows et al, 2010). Reduced expression of LARP1 in HeLa cells led to decreased global protein synthesis rates, and resulted in cell cycle arrest and an inhibition of cell migration (Burrows et al, 2010). Drosophila LARP1 appears to participate in a RNA-binding complex in which LARP1 is associated with 7SK and Bin3 (Bicoid interacting protein 3), a RNA methyltransferase that methylates the 5′ end of 7SK RNA, to serve as a scaffold for PABP and Ago2, which bind directly to mRNAs and negatively regulate initiation of translation (Singh et al, 2011).…”

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

“…In the present study, we found that PDGFRα was strongly down-regulated in both OLs and type II astrocytes, suggesting that PDGFRα is also a key factor in maintaining self-renewal and inhibiting differentiation of OPCs. Transcription factors (TFs) and binding proteins play prominent roles in developmental processes and cell-lineage specification (Ahmed et al 2009;Burrows et al 2010). Here, we found that many OPC-expressed TFs and binding proteins, such as E2F transcription factor 8, pituitary tumortransforming 1 and cell division cycle 20 homolog, were down-regulated in both OLs and type II astrocytes, suggesting they may be involved in maintaining proliferation and self-renewal of OPCs.…”