Ribosome feedback regulation, and growth rate-dependent controls of rRNA synthesis remain to be determined despite numerous investigations. r-protein. REGULATION OF RIBOSOMAL PROTEIN SyNTHESIS. control of ribosomal synthesis can be considered in relation to three basic problems 75.
The rate of cell growth is often in proportion tothe numbers of new ribosomes made (,). It may therefore not come as asurprise to learn that many anticancer drugs interfere with RNA polI transcription or ribosomal RNA (rRNA) metabolism leading topreferential targeting of dividing cancer cells. Inhibition ofribosome biogenesis by chemotherapeutic drugs may contributesignificantly to the efficacy of therapeutic regimens. Ribosomebiogenesis has the potential to be more effectively exploited as atarget in anticancer therapy given that it is one of the majorbiosynthetic activities in a cancer cell. RNA Pol I, themultiprotein complex that synthesizes rRNA, is very active in mostcancer cells (). Selectiveinhibitors of RNA Pol I may therefore offer a general therapeuticstrategy to block cancer cell proliferation and small moleculecompounds that specifically inhibit rDNA transcription have beendeveloped by academic teams and biotech companies (). One compound CX-3543, target rRNAsynthesis by disrupting G-quadruplex DNA structures in the G-richregion of the rRNA repeat, thereby altering the binding of proteinsrequired for rRNA transcription (). A second compound, CX-5461 is aninhibitor of RNA pol I transcription that works by specificallyimpairing the binding of SL1/TIF-1B to the rDNA promoter therebyinhibiting the initiation of rRNA synthesis (). This latter compound selectivelyinhibits Pol I-driven transcription relative to Pol II-driventranscription, DNA replication, and translation. CX-5461selectively kills B-lymphoma cells by induction ofp53-dependent apoptotic signaling (). The small molecule and acridinederivative, BMH-21 was found to have potent antitumorigenicactivity (). BMH-21intercalates into GC-rich sequences in rDNA genes, and repressesRNA Pol I transcription (). Arelated compound, the acridine derivative CID-765471, inhibits rDNAtranscription and activates p53 through 5S RNP also in the absenceof detectable DNA damage ().The mechanism involved in the case of CID-765471 is similar toBMH-21 in that there is a selective degradation of the RPA194subunit of RNA polymerase I. Degradation of RPA194 could be acommon event in the case of nucleolar disruption by non-genotoxicacridines, however it is not a general feature of all rDNAintercalating compounds ().The type of anticancer activity and non-genotoxic activation of p53represented by these different compounds mentioned holds greatpromise in future anticancer therapy, but whether selectivetargeting of ribosome biogenesis will be of broad clinical value inanti-cancer treatment remain to be seen.
Protein Synthesis -Translation and Regulation
Sep 5, 1988. The trmD operon of Escherichia coli encodes the ribosomal proteins S16 and L19, the tRNAm1G37methyltransferase and a 21,000 Mr protein. TRNA, and that the synthesis of ribosomal protein, like the synthesis of rRNA, is subject to the influence of the rel gene control system. In exponentially growing.