Reprogramming the genetic code: The emerging role of ribosomal frameshifting in regulating cellular gene expression

Bioessays. 2016 Jan;38(1):21-6. doi: 10.1002/bies.201500131. Epub 2015 Dec 12.


Reading frame maintenance is a critical property of ribosomes. However, a number of genetic elements have been described that can induce ribosomes to shift on mRNAs, the most well understood of which are a class that directs ribosomal slippage by one base in 5' (-1) direction. This is referred to as programmed -1 ribosomal frameshifting (-1 PRF). Recently, a new -1 PRF promoting element was serendipitously discovered in a study examining the effects of stretches of adenosines in the coding sequences of mRNAs. Here, we discuss this finding, recent studies describing how -1 PRF is used to control gene expression in eukaryotes, and how -1 PRF is itself regulated. The implications of dysregulation of -1 PRF on human health are examined, as are possible new areas in which novel -1 PRF promoting elements might be discovered. Also watch the Video Abstract.

Keywords: NMD; SCA26; cancer; frameshifting; miRNA; polyA track; pseudoknot; ribosome; ribosomopathy; telomere; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cellular Reprogramming / genetics*
  • Frameshifting, Ribosomal / genetics*
  • Gene Expression Regulation / genetics
  • Genetic Code*
  • Humans
  • Protein Biosynthesis / genetics
  • RNA, Messenger / genetics
  • Ribosomes / genetics*


  • RNA, Messenger