A pharmaceutical corporation investigating new therapeutic agents for treatment of Burkitt lymphoma synthesizes a double-stranded RNA molecule that is 21 base pairs in length. The RNA molecule has a base pair sequence that is complementary to a region of mRNA encoding c-Myc. Introduction of the RNA molecule into tumor cells results in a significant reduction in cell growth. Western blot analysis of equivalent numbers of treated and untreated cells is shown below. Which of the following processes was most likely directly interrupted in the cells exposed to the RNA molecule?

Question

A pharmaceutical corporation investigating new therapeutic agents for treatment of Burkitt lymphoma synthesizes a double-stranded RNA molecule that is 21 base pairs in length.  The RNA molecule has a base pair sequence that is complementary to a region of mRNA encoding c-Myc.  Introduction of the RNA molecule into tumor cells results in a significant reduction in cell growth.  Western blot analysis of equivalent numbers of treated and untreated cells is shown below.  Which of the following processes was most likely directly interrupted in the cells exposed to the RNA molecule?

Quizplus · Accepted Answer

11ec160b_377a_356e_9249_e1f32639a597_MD0001_00 The results of the western blot show that the treated cell line produces less c-myc protein. This is most likely due to RNA interference, a mechanism by which short (20-30 base pair) double-stranded RNA sequences induce posttranscriptional gene silencing. Silencing RNA includes both small interfering RNA (siRNA) and microRNA (miRNA). The human genome encodes over 1000 miRNA genes, each one capable of repressing hundreds of target genes; altered expression of miRNA genes are involved in the development of many diseases, including hematologic and solid malignancies. In addition, synthetic siRNA sequences can be introduced into cells to silence specific pathogenic genes (eg, c-Myc oncogene) and are being explored as possible therapeutic agents. After being transcribed, miRNA undergoes processing in the nucleus to form a double-stranded precursor that is then exported into the cytoplasm. There, the precursor is cleaved into a short RNA helix by a ribonuclease protein called dicer. The individual strands are then separated and incorporated into RNA-induced silencing complex (RISC). This multiprotein complex uses its associated miRNA as a template to bind to complementary sequences found on target mRNAs. An exact match generally results in mRNA degradation, but a partial match also causes translational repression by preventing ribosome and translation factor binding. (Choice A) DNA polymerase requires a short nucleic acid sequence primer for initiation of DNA synthesis. During DNA replication, these primers are formed from RNA bases by the enzyme DNA primase. (Choice B) DNA transcription is the process in which RNA is transcribed from a DNA template by an RNA polymerase enzyme. Although certain miRNA sequences can cause transcriptional inhibition, posttranscriptional silencing is the predominant means of RNA interference. (Choice D) Degradation of proteins and polypeptides occurs in proteasomes and lysosomes. Proteasomes mainly degrade nuclear and cytoplasmic proteins; lysosomes degrade cellular organelles and extracellular proteins. (Choice E) Small nuclear RNA (snRNA) molecules bind to specific proteins to form small nuclear ribonucleoproteins (snRNPs). These snRNPs associate with pre-mRNA to form spliceosomes, which function to remove introns from pre-mRNA during processing within the nucleus. Educational objective: Short non-coding RNA sequences (eg, microRNA and small interfering RNA) induce posttranscriptional gene silencing by base-pairing with complementary sequences within target mRNA molecules. __________ References: Origins and mechanisms of miRNAs and siRNAs. (http://www.ncbi.nlm.nih.gov/pubmed/19239886)

A Pharmaceutical Corporation Investigating New Therapeutic Agents for Treatment of Burkitt