103 © The Authors Journal compilation © 2013 Biochemical Society Essays Biochem. (2013) 54, 103–112: doi: 10.1042/BSE0540103 8 Pseudogenes as regulators of biological function Ryan C. Pink and David R.F. Carter 1 School of Life Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3 0BP, U.K. Abstract A pseudogene arises when a gene loses the ability to produce a protein, which can be due to mutation or inaccurate duplication. Previous dogma has dictated that because the pseudogene no longer produces a protein it becomes function- less and evolutionarily inert, being neither conserved nor removed. However, recent evidence has forced a re-evaluation of this view. Some pseudogenes, although not translated into protein, are at least transcribed into RNA. In some cases, these pseudogene transcripts are capable of infuencing the activity of other genes that code for proteins, thereby altering expression and in turn affect- ing the phenotype of the organism. In the present chapter, we will defne pseudo- genes, describe the evidence that they are transcribed into non-coding RNAs and outline the mechanisms by which they are able to infuence the machinery of the eukaryotic cell. Keywords: non-coding RNA, pseudogene, RNA, transcription. 1 To whom correspondence should be addressed (email dcarter@brookes.ac.uk). Introduction A pseudogene is generally defned as a copy of a gene that has lost the capacity to produce a functional protein. Tey were frst discovered in the 1970s when a copy of the 5S rRNA gene was found in Xenopus laevis with homology to the active gene, but with a clear truncation that rendered it non-functional [1]. Sporadic discovery and characterization of pseudogenes over the following 20 years has revealed a number of mechanisms for pseudogene formation [2]. Unitary pseudogenes are formed when spontaneous mutations occur in a coding gene that