Disease relevance of RPL3

• The locus (RP1) for one form of autosomal dominant retinitis pigmentosa (adRP) was mapped on chromosome 8q11-q22 between D8S589 and D8S285, which are about 8 cM apart, by linkage analysis in an extended family ascertained in the USA [1].
• Mobilizable shuttle plasmids containing the origin-of-transfer (oriT) region of plasmids F (IncFI), ColIb-P9 (IncI1), and RP4/RP1 (IncPalpha) were constructed to test the ability of the cognate conjugation system to mediate gene transfer from Escherichia coli to Saccharomyces cerevisiae [2].
• In a follow-up study in which rats were gavaged with 2000 mg/kg RP-1, submaxillary gland hypertrophy did not occur [3].

High impact information on RPL3

• In an attempt to establish the mechanisms responsible for such balanced synthesis we have altered the gene dosage for one of the components by introducing into yeast an autonomously replicating plasmid containing the gene tcm1, which codes for ribosomal protein L3 [4].
• RNase mapping of transcripts from pap1-1 cells revealed PAB1 mRNA to be poly(A)- whereas TCM1 exists as equal amounts of poly(A)- and poly(A)+ mRNA 60 min after shift [5].
• Interestingly, both of these classes of TCM1 mRNA appear in similar amounts in each polyribosome fraction indicating that ribosomes may not distinguish between them [5].
• NOP2 mRNA levels also increase during the onset of growth, accompanied by a similar increase in the levels of TCM1 mRNA [6].
• Of six independently isolated tcm1 mutants, five were clearly mak-, and the sixth was weakly mak-. In each case, the mak- phenotype and the trichodermin-resistant phenotypes cosegregated in meiosis and showed the expected tight linkage to pet17 [7].

Biological context of RPL3

• Transient depletion of the human homologues GRWD, Pescadillo, Rpl3, Bop1 and Orc6L resulted in an increase of abnormal mitoses with appearance of binucleate or hyperploid cells, of cells with multipolar spindles and of aberrant metaphase plates [8].
• The mak8-1 allele of RPL3 contains two adjacent missense mutations which are predicted to structurally alter the Mak8-1p [9].
• Mutations in the RPL3 gene, which encodes a ribosomal protein located at the peptidyltransferase center, promote approximately three- to fourfold increases in programmed -1 ribosomal frameshift efficiencies and loss of the M1 killer virus of yeast [9].
• Furthermore, we have demonstrated that the Rap1p-truncation affects the repression of TCM1 , encoding ribosomal protein L3, which has no Rap1p-binding site in its upstream regulatory region [10].
• To understand how expression of ribosomal protein genes is regulated in plants, we altered expression of the large subunit ribosomal protein L3 (RPL3) genes in Nicotiana tabacum using post-transcriptional gene silencing (PTGS) [11].

Anatomical context of RPL3

• In a shift to the nonpermissive temperature, ts352 (cca1-1) cells rapidly cease protein synthesis, reduce the rates of degradation of the CDC4, TCM1, and PAB1 mRNAs three- to fivefold, and increase the relative number of ribosomes associated with mRNAs and the overall size of polysomes [12].
• Decreasing RPL3 gene expression resulted in a decrease in accumulation of the pre-rRNA, establishing a prominent role for L3 in ribosome biogenesis in plants [11].

Associations of RPL3 with chemical compounds

• Yeast cells unable to transcribe tcm1 or cyh2 without galactose did not grow [13].
• The mutation to trichodermin resistance conferred resistance to other 12,13-epoxytrichothecenes and to the structurally unrelated antibiotic anisomycin [14].
• It was estimated that the large subunit contained about 10 protein-bound methyl groups distributed mainly among proteins YL23, YL32 and YL1 [15].

Other interactions of RPL3

• We also showed that overexpression of RRB1 led to an increase in the expression of RPL3 while all other examined RP genes were unaffected [16].
• We placed a regulatory sequence derived from the GAL10 locus of Saccharomyces cerevisiae at various distances from the start sites of transcription of two yeast ribosomal protein genes, tcm1 and cyh2 [13].
• Effects of progressive depletion of TCM1 or CYH2 mRNA on Saccharomyces cerevisiae ribosomal protein accumulation [17].

References