Abstract
Evolution and Complexity of Micro RNA in the Human Brain
Highlights
Up-regulated micro RNAs (miRNAs) in human brain-specific neurodegenerative disorders such as Alzheimer’s disease (AD) may help explain the large number of essential brain gene messages observed to be significantly down-regulated in AD affected anatomical regions, such as in the temporal lobe neocortex (Brodmann area 22) and hippocampus, or in primary human brain cell cultures that are chronically subjected to AD-relevant stressors (Loring et al, 2001; Colangelo et al, 2002; Lukiw, 2004, 2012; Lukiw and Pogue, 2007; Sethi and Lukiw, 2009; Ginsberg et al, 2012; Lukiw and Alexandrov, 2012; Lukiw et al, 2012; Wang et al, 2012)
NAs is surprisingly far less; for example only about one-thirtieth of all so far identified human miRNAs are abundantly present in the human brain association neocortex (Table 1)
Mathematical, bioinformatical, and nucleotide sequence analysis indicate that a 22 nt single stranded RNA composed of four different ribonucleotides (A, G, C, and U) may have as many as 1013 possible sequence combinations, so the fact that there typically only on the scale of ∼102 abundant miRNAs in any single human brain sample suggests a very high developmental and evolutionary selection pressure to utilize only specific miRNA oligonucleotide sequences that will yield neurobiologically useful miRNA–messenger RNAs (mRNAs) interactions (Lukiw, 2012; Lukiw and Alexandrov, 2012)
Summary
The discovery of small non-coding RNAs (sncRNAs), and the biological actions of these ribonucleotide entities in the developing, aging, and pathological human central nervous system (CNS) has opened a novel and fascinating vista into our appreciation of human brain epigenetics, the role of sncRNAs on homeostatic and pathogenic gene control, and the potential role of single stranded, 22 nt signals in shaping the transcriptome of the human CNS (Lukiw et al, 1992; Ambros, 2004, 2011; Lukiw, 2007; Lukiw and Pogue, 2007; Guo et al, 2010). The primary mode of action of miRNAs is to bind to target ribonucleotide sequences in messenger RNAs (mRNAs), typically in their 3′ un-translated region (3′-UTR), resulting in a highly selective repression of the readout of that mRNA’s genetic information (Lukiw, 2007; Guo et al, 2010; Ambros, 2011).
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