BackgroundAdenosine-to-inosine RNA editing is a highly conserved process that post-transcriptionally modifies mRNA, generating proteomic diversity, particularly within the nervous system of metazoans. Transcripts encoding proteins involved in neurotransmission predominate as targets of such modifications. Previous reports suggest that RNA editing is responsive to environmental inputs in the form of temperature alterations. However, the molecular determinants underlying temperature-dependent RNA editing responses are not well understood.ResultsUsing the poikilotherm Drosophila, we show that acute temperature alterations within a normal physiological range result in substantial changes in RNA editing levels. Our examination of particular sites reveals diversity in the patterns with which editing responds to temperature, and these patterns are conserved across five species of Drosophilidae representing over 10 million years of divergence. In addition, we show that expression of the editing enzyme, ADAR (adenosine deaminase acting on RNA), is dramatically decreased at elevated temperatures, partially, but not fully, explaining some target responses to temperature. Interestingly, this reduction in editing enzyme levels at elevated temperature is only partially reversed by a return to lower temperatures. Lastly, we show that engineered structural variants of the most temperature-sensitive editing site, in a sodium channel transcript, perturb thermal responsiveness in RNA editing profile for a particular RNA structure.ConclusionsOur results suggest that the RNA editing process responds to temperature alterations via two distinct molecular mechanisms: through intrinsic thermo-sensitivity of the RNA structures that direct editing, and due to temperature sensitive expression or stability of the RNA editing enzyme. Environmental cues, in this case temperature, rapidly reprogram the Drosophila transcriptome through RNA editing, presumably resulting in altered proteomic ratios of edited and unedited proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-014-0111-3) contains supplementary material, which is available to authorized users.
Multiple sclerosis (MS) is a common autoimmune disease of central nervous system in which neurodegenerative and inflammatory mechanisms cause alternate neurological impairments. Many inflammatory and anti-inflammatory cytokines were suggested as contributor in MS pathogenesis, and the balance between these opposing cytokines can regulate MS severity. IL-37, an anti-inflammatory cytokine, is the most recently identified member of IL-1 family, which acts as a natural inhibitor of innate immunity. However, the role of IL-37 in MS has not investigated so far. Therefore, in this study, we aimed to measure serum level of IL-37 in patients with relapsing remitting multiple sclerosis (RRMS) and neuromyelitis optica (NMO). In a case-control study, plasma was collected from healthy controls (n = 49) and also patients with RRMS (n = 122) and NMO (n = 31). Serum level measurement of IL-37 was performed using enzyme-linked immunoassay (ELISA) method. The serum levels of IL-37 were 247.46 ± 74.02 and 312.00 ± 86.72 and 114.63 ± 20.58 in RRMS and NMO patients and healthy controls, respectively, showing statistically significant difference between them (P = 0.00). Furthermore, we found a positive correlation between the serum levels of IL-37 and EDSS of patients (r = +0.31 and P = 0.00). In summary, the serum level of IL-37 was found to be significantly increased in MS patients compared to healthy controls. Furthermore, the mean serum level of IL-37 was correlated with disease severity. This suggests that IL-37 may be part of a feed-back loop to control underlying inflammation in MS pathogenesis. However, further studies will be required to indicate exact role of IL-37 in the MS pathomechanisms.
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