Analysis of energetically biased transcripts of viruses and transposable elements

Genetics and Molecular Biology

Rodrigo Secolin²  Vinícius D'Ávila Bitencourt Pascoal²  Iscia Lopes-cendes²  Tiago Campos Pereira¹ 

[1] ,Universidade de Campinas Faculdade de Ciências Médicas Departamento Genética MédicaCampinas SP ,Brazil

关键词: RNAi;    siRNA;    synonymous mutation;    viral evolution;   

DOI  :  10.1590/S1415-47572012005000078

来源: SciELO

【 摘 要 】

RNA interference (RNAi) is a natural endogenous process by which double-stranded RNA molecules trigger potent and specific gene silencing in eukaryotic cells and is characterized by target RNA cleavage. In mammals, small interfering RNAs (siRNAs) are the trigger molecules of choice and constitute a new class of RNA-based antiviral agents. In an efficient RNAi response, the antisense strand of siRNAs must enter the RNA-induced silencing complex (RISC) in a process mediated by thermodynamic features. In this report, we hypothesize that silent mutations capable of inverting thermodynamic properties can promote resistance to siRNAs. Extensive computational analyses were used to assess whether continuous selective pressure that promotes such mutations could lead to the emergence of viral strains completely resistant to RNAi (i.e., prone to transfer only the sense strands to RISC). Based on our findings, we propose that, although synonymous mutations may produce functional resistance, this strategy cannot be systematically adopted by viruses since the longest RNAi-refractory sequence is only 10 nt long. This finding also suggests that all mRNAs display fluctuating thermodynamic landscapes and that, in terms of thermodynamic features, RNAi is a very efficient antiviral system since there will always be sites susceptible to siRNAs.

【 授权许可】

CC BY   
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