N1-methylation of adenosine (mA) in ND5 mRNA leads to complex I dysfunction in Alzheimer's disease.

One mechanism of particular interest to regulate mRNA fate post-transcriptionally is mRNA modification. Especially the extent of mA mRNA methylation is highly discussed due to methodological differences. However, one single mA site in mitochondrial ND5 mRNA was unanimously reported by different groups.

Mitochondrial Dysfunction as a Causative Factor in Alzheimer's Disease-Spectrum Disorders: Lymphocytes as a Window to the Brain.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. Today, AD affects millions of people worldwide and the number of AD cases will further increase with longer life expectancy. The AD brain is marked by severe neurodegeneration, such as the loss of synapses and neurons, atrophy and depletion of neurotransmitter systems, especially in the hippocampus and cerebral cortex.

RNA marker modifications reveal the necessity for rigorous preparation protocols to avoid artifacts in epitranscriptomic analysis.

The accurate definition of an epitranscriptome is endangered by artefacts resulting from RNA degradation after cell death, a ubiquitous yet little investigated process. By tracing RNA marker modifications through tissue preparation protocols, we identified a major blind spot from daily lab routine, that has massive impact on modification analysis in small RNAs. In particular, m6,6A and Am as co-varying rRNA marker modifications, appeared in small RNA fractions following rRNA degradation in vitro and in cellulo.

Manganese Ions Individually Alter the Reverse Transcription Signature of Modified Ribonucleosides.

Reverse transcription of RNA templates containing modified ribonucleosides transfers modification-related information as misincorporations, arrest or nucleotide skipping events to the newly synthesized cDNA strand. The frequency and proportion of these events, merged from all sequenced cDNAs, yield a so-called RT signature, characteristic for the respective RNA modification and reverse transcriptase (RT). While known for DNA polymerases in so-called error-prone PCR, testing of four different RTs by replacing Mg with Mn in reaction buffer revealed the immense influence of manganese chloride on derived RT signatures, with arrest rates on mA positions dropping from 82% down to 24%.