MicroRNAs and inappropriate functions

By: James V. Kohl | Published on: June 4, 2015

Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w

Highlights

  • miRNAs are oxidized by ROS
  • Oxidized miR-184 mismatches with the 3′ UTRs of Bcl-xL and Bcl-w
  • Oxidized miR-184 promotes apoptosis via suppressing Bcl-xL and Bcl-w
  • Oxidized miR-184 increases the susceptibility of the heart to I/R injury

Summary

MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (3′ UTRs) of target mRNA transcripts, thereby inhibiting mRNA translation or promoting mRNA degradation. Excessive reactive oxygen species (ROS) can cause cell-damaging effects through oxidative modification of macromolecules leading to their inappropriate functions. Such oxidative modification is related to cancers, aging, and neurodegenerative and cardiovascular diseases. Here we report that miRNAs can be oxidatively modified by ROS. We identified that miR-184 upon oxidative modification associates with the 3′ UTRs of Bcl-xL and Bcl-w that are not its native targets. The mismatch of oxidized miR-184 with Bcl-xL and Bcl-w is involved in the initiation of apoptosis in the study with rat heart cell line H9c2 and mouse models. Our results reveal a model of ROS in regulating cellular events by oxidatively modifying miRNA.
My comment: The need for the anti-entropic epigenetic effects of nutrient-dependent microRNAs as anti-oxidants would be clear if they reported the role of viruses and viral microRNAs in the context of RNA-mediated cell type differentiation. Viral microRNAs link entropic elasticity to genomic entropy when the anti-entropic epigenetic effects of nutrient-dependent microRNAs is reduced by nutrient stress or social stress. Nutrient stress includes eating too much, which helps to explain the obvious link from obesity to cancer and other pathology.
See also:

MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium

Excerpt:
A large body of work has established that microRNAs (miRNAs), small non-coding RNAs that function in post-transcriptional gene regulation, act as oncogenes or tumor suppressors in a variety of tissues, and their deregulation can lead to cancer [19,20]. MiRNA gene loci are transcribed by RNA polymerase II to generate primary (pri-) miRNA transcripts, which are then cleaved by the nuclear RNAse DROSHA complex to form stem-loop precursor (pre-) miRNAs. Following nuclear export to the cytoplasm, pre-miRNAs undergo further processing by the DICER complex to generate mature miRNAs, which typically bind to the 3’ untranslated region of target messenger RNAs (mRNAs) and mediate translational repression or RNA degradation. MiRNAs have been linked to inflammatory pathways [21,22], which are likely to play important roles in BE/EA. Changes in miRNA expression have been detected at multiple stages in the development of EA [23–38], and certain miRNAs may be associated with prognosis [33,35].
My comment: Similarly, a body of work has established the link from viral microRNAs to pathology. That body of work links viruses to pathology via the inability of nutrient-dependent microRNAs to repair DNA via RNA-mediated amino acid substitutions during life history transitions.


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