Pseudogene - Possible Functional Pseudogenes

Possible Functional Pseudogenes

By definition, pseudogenes lack a function. However, the classification of pseudogenes generally relies on computational analysis of genomic sequences using complex algorithms. This has led to the incorrect identification of pseudogenes. Examples include

1. The Drosophila jingwei gene, a functional, chimeric gene which was once thought to be a processed pseudogene.
2. Makorin1 (MKRN1). In 2003, Hirotsune et al. identified a retrotransposed pseudogene whose transcript purportedly plays a trans-regulatory role in the expression of its homologous gene, Makorin1 (MKRN1) (see also RING finger domain and ubiquitin ligases), and suggested this as a general model under which pseudogenes may play an important biological role. Hirotsune's report prompted two molecular biologists to carefully review scientific literature on the subject of pseudogenes. To the surprise of many, they found a number of examples in which pseudogenes play a role in gene regulation and expression, forcing Hirotsune's group to rescind their claim that they were the first to identify pseudogene function. Furthermore, the original findings of Hirotsune et al. concerning Makorin1 have recently been strongly contested; thus, the possibility that some pseudogenes could have important biological functions was disputed.
3. Phosphoglycerate mutase 3 (PGAM3P). A processed pseudogene called phosphoglycerate mutase 3 (PGAM3P) actually produces a functional protein.
4. siRNAs. Some endogenous siRNAs appear to be derived from pseudogenes, and thus some pseudogenes play a role in regulating protein-coding transcripts.
5. PTENP1 and KRAS1P. In June 2010, Nature published an article showing the mRNA levels of tumour suppressor PTEN and oncogenicKRAS is affected by their pseudogenes PTENP1 and KRAS1P. This discovery demonstrated an miRNA decoy function for pseudogenes and identified their transcripts as biologically active units in tumor biology; thus attributing a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs in disease progression.