RNA editing, DNA recoding and the evolution of human cognition

Mattick, John S.; Mehler, Mark F.

doi:10.1016/j.tins.2008.02.003

Cited by 141 publications

(190 citation statements)

References 80 publications

Supporting

Mentioning

184

Contrasting

Unclassified

Order By: Relevance

“…(95) An alternative interpretation of these observations is that Alu elements provided an important platform for the expansion of RNA editing in primates, driven by and underpinning the development of higher order cognition. (94) Since most of these edited elements occur in non-coding sequences, one presumes that they are largely regulatory, affecting brain development and function. Alu RNAs have been shown to act as transacting transcriptional repressors by binding RNA polymerase II (96) and to be involved in the regulation of alternative splicing, translation and mRNA stability.…”

Section: Review Articlementioning

confidence: 99%

RNA regulation of epigenetic processes

et al. 2009

Self Cite

View full text Add to dashboard Cite

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations.

show abstract

Section: Review Articlementioning

confidence: 99%

RNA regulation of epigenetic processes

et al. 2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…15 ). However, this could not be tested because of the unavailability of a suitable patient material.…”

Section: Ohtahara Syndrome and Arx T Fullston Et Almentioning

confidence: 99%

Ohtahara syndrome in a family with an ARX protein truncation mutation (c.81C>G/p.Y27X)

et al. 2009

View full text Add to dashboard Cite

Aristaless-related homeobox (ARX) gene mutations cause a diverse spectrum of disorders of the human brain, including lissencephaly, various forms of epilepsy and non-syndromic mental retardation. We have identified a novel mutation, c.81C4G (p.Y27X), within the ARX gene in a family with two affected male cousins. One of the boys was diagnosed with an early infantile epileptic encephalopathy also known as Ohtahara syndrome, whereas his cousin had been diagnosed with West syndrome (WS). Both patients have normal genitalia and neither have lissencephaly. The ARX mutation identified is predicted to yield a severely truncated protein of only 26 amino acids and can be considered as a null mutation. Somewhat surprisingly, however, it does not yield the X-linked lissencephaly with ambiguous genitalia (XLAG) syndrome. We proposed that the ARX mRNA translation re-initiated at the next AUG codon at position c.121-123 (aa 41) and, thus, partly rescued these patients from XLAG. Our in vitro studies show that this N-terminally truncated ARX protein (p.M41_C562) is detected by western immunoblot in lysates from cells transiently transfected with an ARX over-expression construct containing the c.81C4G mutation. Although these findings widen the spectrum of clinical phenotypes because of mutations in the ARX gene, they also emphasize the molecular pathogenetic effect of individual mutations as well as the effect of genetic background resulting in intrafamilial clinical heterogeneity for these mutations.

show abstract

“…31 As the inverted Alus embedded in pre/mRNA are substrates for editing and the level of editing is substantially increased in human vs. mice, the editing in Alus may have direct roles in the advanced neuronal development in human. 32 Additionally, genomic sequencing and mapping among human populations demonstrate that Alus and Alu related polymorphisms contribute greatly to the diversity among humans.…”

Section: The Function Of Non-transcribed Genomic Alusmentioning

confidence: 99%

“…This inclusion has since been adapted as a part of isoforms of the deaminase and is highly expressed in neuronal tissues. 76 Mattick and Mehler 32 proposed that the adaptation of Alus through selection could contribute to the higher order of cognitive function in humans. The Alus could be the critical element that sets human apart from other primates.…”

mentioning

confidence: 99%