Alterations in ribosomal protein L19 that decrease the fidelity of translation

Abstract

Ribosomal protein L19 is an essential ribosomal protein and is a component of bridge B8, one of the protein-RNA bridges linking the large and small ribosomal subunits. Bridge B8 also contributes to the accuracy of translation by affecting GTPase activation by ribosome-bound aminoacyl tRNA-EF-Tu•GTP ternary complexes. Previous work has identified a limited number of accuracy-altering alterations in protein L19 of Salmonella enterica and Thermus thermophilus. Here, we have targeted the Escherichia coli rplS gene encoding L19 for mutagenesis and have screened for mutants with altered levels of miscoding. We have recovered 14 distinct L19 mutants, all of which promote increased stop codon readthrough, but do not have major effects on subunit association or cell growth. Examination of the E. coli 70S ribosome structure indicates that the amino acid substitutions cluster in three distinct regions of L19 and thereby potentially affect its interactions with L14 and 16S rRNA.

In silico Prediction of New Drug Candidates Against the Multidrug-Resistant and Potentially Zoonotic Fish Pathogen Serotype III Streptococcus agalactiae

“…The phosphorylation of ribosomal proteins can reduce up to 50% of their activity ( Mikulík et al, 2001 ), although it seems that phosphorylated L19 is the active form of the protein that contribute to the assembly and decoding processes ( Soung et al, 2009 ). Moreover, a mutagenic study of the rplS gene in E. coli revealed that, despite the restraint in translation, the defective mutants did not exhibit problems in 30S–50S association or cell growth ( VanNice et al, 2016 ). There is no record of L19 protein as a drug target in the DrugBank database.…”

Heavy metal sensitivities of gene deletion strains for ITT1 and RPS1A connect their activities to the expression of URE2, a key gene involved in metal detoxification in yeast

“…Examples of genes that formed GIs with ITT1 and RPS1A are large ribosomal subunit protein 19A ( RPL19A ) and general control non-derepressible ( GCN3 ), respectively. Rpl19p is a conserved large ribosomal subunit protein involved in ribosomal intersubunit bridging and its alteration is connected to the fidelity of translation [ 54 ], [ 55 ]. On the other hand, GCN3 is the alpha subunit of translation initiation factor 2B (eIF2B), which is involved in guanine-nucleotide exchange for eIF2.…”

Heavy metal sensitivities of gene deletion strains forITT1andRPS1Aconnect their activities to the expression ofURE2, a key gene involved in metal detoxification in yeast

“…Examples of genes that formed GIs with ITT1 and RPS1A are large ribosomal subunit protein 19A (RPL19A) and general control non-derepressible (GCN3), respectively. Rpl19p is a conserved large ribosomal subunit protein involved in ribosomal intersubunit bridging and its alteration is connected to the fidelity of translation [54], [55]. On the .…”