Year: 2015
Type: article
Abstract: SpringerPlus 2015, 4(Suppl 1):L1 MicroRNAs (miRNAs) are short, 22-25 nucleotide long transcripts that may suppress entire signaling pathways by interacting with the 3'-untranslated region (3'-UTR) of coding mRNA targets, interrupting translation and inducing degradation of these targets.The long 3'-UTRs of brain transcripts compared to other tissues predict important roles for brain miRNAs.Supporting this notion, we found that brain miRNAs co-evolved with their target transcripts, that non-coding pseudogenes with miRNA recognition elements compete with brain coding mRNAs on their miRNA interactions, and that Single Nucleotide Polymorphisms (SNPs) on such pseudogenes are enriched in mental diseases including autism and schizophrenia, but not Alzheimer's disease (AD).Focusing on evolutionarily conserved and primate-specifi c miRNA controllers of cholinergic signaling ('CholinomiRs'), we fi nd modifi ed CholinomiR levels in the brain and/or nucleated blood cells of patients with AD and Parkinson's disease, with treatment-related diff erences in their levels and prominent impact on the cognitive and anti-infl ammatory consequences of cholinergic signals.Examples include the acetylcholinesterase (AChE)-targeted evolutionarily conserved miR-132, whose levels decline drastically in the AD brain.Furthermore, we found that interruption of AChE mRNA's interaction with the primatespecifi c CholinomiR-608 in carriers of a SNP in the AChE's miR-608 binding site induces domino-like eff ects that reduce the levels of many other miR-608 targets.Young, healthy carriers of this SNP express 40% higher brain AChE activity than others, potentially aff ecting the responsiveness to AD's anti-AChE therapeutics, and show elevated trait anxiety, infl ammation and hypertension.Non-coding regions aff ecting miRNA-target interactions in neurodegenerative brains thus merit special attention.
Source: SpringerPlus
Author: Philip Beart
Institution: The University of Melbourne
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
Funders: Giovanni Armenise-Harvard Foundation, National Research Centre, Sihtasutus Archimedes, Eesti Teaduste Akadeemia, Acorda Therapeutics, Alkoholitutkimussäätiö, European Commission, University of Nottingham, Agence Nationale de la Recherche, Grantová Agentura České Republiky, Russian Foundation for Basic Research, Eesti Teadusagentuur, Austrian Science Fund, Cancerfonden, Fondazione Cariplo, Ministero della Salute, Israel Science Foundation, Karolinska Institutet, Vetenskapsrådet, Agentúra na Podporu Výskumu a Vývoja, Uniwersytet Łódzki, Vedecká Grantová Agentúra MŠVVaŠ SR a SAV, Stichting Kinderen Kankervrij, Barncancerfonden, Hersenstichting, Pirkanmaan Sairaanhoitopiiri, National Institutes of Health, Narodowe Centrum Badań i Rozwoju, European Regional Development Fund, Krajowy Naukowy Osrodek Wiodacy, State Education Development Agency Republic of Latvia
Awards: G140429316, G2210244462, G2225487304, G272430482, G2785730575, G3043352584, G3491454501, Novel Optical Biosensing Systems and Their Biomedical Applications, Signal Processing in Neurons, Diabetic peripheral neuropathy: relationships between neuroactive steroids and myelin lipid synthesis, Neurobiology of social interaction as an alternative to drugs of abuse, Impact of blunted fatty acid synthesis on the development of diabetic peripheral neuropathy: deciphering the role of the lipogenic factor SREBP-1c, G5077087964, G5529599431, G6225324163, Regulation of gene expression and signaling in nervous system health and disease, Social interaction as an alternative to cocaine, G7677202330, G9000192668
OpenAlex ID: W1570755280