Key result
Higher-order RNA structures in the plus strand mediate efficient subgenomic mRNA transcription in Tombusviruses, a process that can be artificially controlled using small-molecule RNA aptamers.
Provides mechanistic insights into Tombusvirus subgenomic mRNA transcription and demonstrates a novel approach to artificially regulate this process using small molecules.
Should not yet influence clinical practice; leaves open whether this viral transcription mechanism can be targeted for.
Subgenomic (sg) mRNAs are small viral messages that are synthesized by polycistronic positive-strand RNA viruses to allow for the translation of certain viral proteins. Tombusviruses synthesize two such sg mRNAs via a premature termination mechanism. This transcriptional process involves the viral RNA-dependent RNA polymerase terminating minus-strand RNA synthesis prematurely at internal RNA signals during copying of the viral genome. The 3'-truncated minus-strand RNAs generated by the termination events then serve as templates for sg mRNA transcription. A higher-order RNA structure in the viral genome, located just upstream from the termination site, is a critical component of the RNA-based polymerase attenuation signal. Here, we have analyzed the role of this RNA structure in mediating efficient sg mRNA2 transcription. Our results include the following: (i) we define the minimum overall thermodynamic stability required for an operational higher-order RNA attenuation structure; (ii) we show that the distribution of stability within an attenuation structure affects its function; (iii) we establish that an RNA quadruplex structure can act as an effective attenuation structure; (iv) we prove that the higher-order RNA structure forms and functions in the plus strand; (v) we provide evidence that a specific attenuation structure-binding protein factor is not required for transcription; (vi) we demonstrate that sg mRNA transcription can be controlled artificially through small-molecule activation using RNA aptamer technology. These findings provide important new insights into the premature termination mechanism and present a novel approach to regulate the transcriptional process.
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Wang et al. (2008) studied Tombusvirus subgenomic mRNA transcription. Small-molecule activation using RNA aptamer technology was evaluated on Subgenomic mRNA2 transcription efficiency and mechanism. Higher-order RNA structures in the plus strand mediate efficient subgenomic mRNA transcription in Tombusviruses, a process that can be artificially controlled using small-molecule RNA aptamers.
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