Circular RNA (circRNA) in Alzheimer's disease (AD) - PubMed (original) (raw)

Circular RNA (circRNA) in Alzheimer's disease (AD)

Walter J Lukiw. Front Genet. 2013.

No abstract available

Keywords: Alzheimer's disease; circular RNAs; evolution; gene regulation; hippocampal CA1; miRNA-7; micro RNA; transcriptome.

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Figure 1

Figure 1

(A) Detection of circRNA for miRNA-7 (ciRS-7) in sporadic Alzheimer's disease (AD) and age-matched control hippocampal CA1 [control (C) N = 4; AD (A) N = 6]; the single upper ciRS-7 (~1400 nt) band contains ~70 selectively conserved miRNA-7 binding sites as previously described (Hansen et al., 2013); a lower 28S RNA served as an internal loading control; all samples depleted of rRNA were treated with 50 units of RNaseR prior to electrophoresis RNaseR is a processive, Mg++-dependent hydrolytic exoribonuclease that degrades linear but not circular RNA; see Hansen et al. (2013); predicted circular transcripts consistently resisted an RNaseR challenge; 30 ug total AD and control hippocampal CA1 RNA was separated on agarose gels, transferred and probed with biotinylated or radiolabeled miRNA-7 probes as previously described (Colangelo et al., ; Hansen et al., 2013); detection was performed using a nonisotopic BrightStar BioDetect Kit (Ambion, Austin, TX; detection limit ~100 fg) or by standard autoradiography (Lukiw et al., 1992); (B) AD ciRS-7 is significantly reduced to about 0.18-fold of control (con) in a study of 20 control and AD (AD) hippocampal CA1 samples; this implicates loss of miRNA-7 sponge effects, an ambient up-regulation of miRNA-7 (as is observed), and down-regulation of a family of miRNA-7-sensitive mRNAs in the sporadic AD brain; other circRNAs may be involved; there were no significant differences between age for control or AD tissues [mean ± 1 standard deviation (SD) = 75.4 ± 8.3 year vs. 77.5 ± 7.6 year]; all AD cases were for moderate-to-advanced stages of AD; all post-mortem intervals were 2.1 h or less (Colangelo et al., 2002); there were no significant differences in age, ApoE allele status, RNA quality (all RIN values were 8.1–9.0) or yield between the control or AD groups (p > 0.05, ANOVA); a dashed horizontal line at 1.0 indicates homeostatic (control) ciRS-7 levels for ease of comparison; *p < 0.001 (ANOVA).

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References

    1. Bingol B., Sheng M. (2011). Deconstruction for reconstruction: the role of proteolysis in neural plasticity and disease. Neuron 69, 22–32 10.1016/j.neuron.2010.11.006 - DOI - PubMed
    1. Burmistrova O. A., Goltsov A. Y., Abramova L. I., Kaleda V. G., Orlova V. A., Rogaev E. I. (2007). MicroRNA in schizophrenia: genetic and expression analysis of miR-130b (22q11). Biochemistry (Mosc). 72, 578–582 10.1134/S0006297907050161 - DOI - PubMed
    1. Cogswell J. P., Ward J., Taylor I. A., Waters M., Shi Y., Cannon B., et al. (2008). Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways. J. Alzheimers Dis. 14, 27–41 - PubMed
    1. Colangelo V., Schurr J., Ball M. J., Pelaez R. P., Bazan N. G., Lukiw W. J. (2002). Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J. Neurosci. Res. 70, 462–473 10.1002/jnr.10351 - DOI - PubMed
    1. Ginsberg S. D., Alldred M. J., Che S. (2012). Gene expression levels assessed by CA1 pyramidal neuron and regional hippocampal dissections in Alzheimer's disease. Neurobiol. Dis. 45, 99–107 10.1016/j.nbd.2011.07.013 - DOI - PMC - PubMed

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