Question

2. There are multiple ways to control translation once a transcript is made. Please list at least 5 ways in which translation can be regulated at the initiation level. Provide an example for each, and explain why this type of regulation is either global or gene-specific.

Answer 1

Translation is the process of translating the sequence of a messenger RNA (mRNA) molecule to a sequence of amino acids during protein synthesis.

• One class of bacterial regulatory RNAs (called sRNAs) acts in trans to control translation of target genes. Their size range from 80-110 nucleotides and are encoded in their final form by small genes. Most sRNAs work by base pairing with complementary sequences within target mRNAs and directing destruction of the mRNA, inhibiting its translation. Binding of an sRNA to its target mRNA is aided by the bacterial protein Hfq. This RNA chaperone is needed because of the complementarity between the sRNAs and their target mRNAs is typically imperfect and short, and thus their interaction is weak. Hfq facilitates base pairing and increases stability of the regulators even before the sRNAs are paired with their targets. Example; 81-nucleotide RybB RNA from E.coli. This sRNA binds several target mRNA and triggers their destruction because the double-strand stretch of heteroduplex formed upon pairing is recognized as substrate by the hexonuclease RNase E.

Figure: Activation and repression of translation by sRNAs. When the ribosome binding site (RBS) is occluded by base pairing with another RNA molecule (as in part b) or another region of the same RNA molecule (as in part a), translation is inhibited.

• Riboswitches reside within the transcripts of genes that control gene expression in response to changes in the concentrations of small molecules. These regulatory elements are typically found within the 5'-untranslated regions (5'-UTRs) of the genes they control, and they can regulate expression at the level of transcription or translation. They do this through changes in RNA secondary structure. Each riboswitch is made up of two components: the aptamer and the expression platform. The aptamer binds the small-molecule ligand and, in response, undergoes a conformational change, which, in turn, causes a change in the secondary structure of the adjoining expression platform. These conformational changes alter expression of the associated gene by either terminating transcription or inhibiting the initiation of translation.

Figure 2: Organization of riboswitch RNAs. The aptamer binds the controlling metabolite, causing changes in the structure of the adjoining expression platform.

Figure 3: Riboswitches regulate transcription termination or translation initiation. Two examples of a SAM-sensing riboswitch, (a) regulating transcription termination, in the other (b) translation intiation termination.