10. Transcription

siRNAs target a variety of different RNA transcripts for degradation.

Which of the following enzymes are responsible for cleaving and processing miRNAs and siRNAs?

MiRNAs and siRNAs target degradation of RNA transcripts by binding to what?

In 1998, future Nobel laureates Andrew Fire and Craig Mello, and colleagues, published an article in Nature entitled, 'Potent and Specific Genetic Interference by Double-Stranded RNA in Caenorhabditis elegans.' Explain how RNAi is both 'potent and specific.'

Present an overview of RNA interference (RNAi). How does the silencing process begin, and what major components participate?

RNAi may be directed by small interfering RNAs (siRNAs) or microRNAs (miRNAs); how are these similar, and how are they different?

miRNAs target endogenous mRNAs in a sequence-specific manner. Explain, conceptually, how one might identify potential mRNA targets for a given miRNA if you only know the sequence of the miRNA and the sequence of all mRNAs in a cell or tissue of interest.

In principle, RNAi may be used to fight viral infection. How might this work?

While miRNA response elements (MREs) may be located anywhere within an mRNA, they are most often found outside the coding region in the 5' or 3' UTR. Explain why this is likely the case given that miRNAs often target more than one mRNA.

RNAi is currently being tested as a therapeutic tool for genetic diseases and other conditions. Consider the following: cystic fibrosis caused by loss of function of the CFTR gene, HIV infection, and cancer caused by hyperactivity of a growth factor receptor. Which of these may be treatable by RNAi, and which not? Explain your reasoning.

Explain how the expression of a single gene can be quickly, efficiently, and specifically shut down at the transcriptional, posttranscriptional, and posttranslational stages through the coordinated expression of a transcriptional repressor, an miRNA, and a ubiquitin ligase.