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Walz, L.

Publications and source records attributed to Walz, L..

2 recordsLinked to original sources

ModiDeC: a multi-RNA modification classifier for direct nanopore sequencing

RNA modifications play a crucial role in various cellular functions. Here, we present ModiDeC, a deep-learning-based classifier able to identify and distinguish multiple RNA modifications (N6-methyladenosine, inosine, pseudouridine, 2'-O-methylguanosine, and N1-methyladenosine) using direct RNA sequencing. Alongside ModiDeC, we provide an extensive database of in vitro-transcribed and synthetic sequences generated with both the new RNA004 chemistry and the old RNA002 kit. We show that RNA modifications can be accurately recognized and distinguished across different sequence motifs using synthetic data as well as in HEK293T cells and human blood samples. ModiDeC comes with a graphical user interface that allows easy customization and adaptation to specific research questions, such as learning and classifying additional RNA modifications and further sequence motifs. The reproducibility across samples, together with the low rate of false positives, underscores the potential of ModiDeC as a powerful tool for advancing the analysis of epitranscriptomes and RNA modification.

bioinformatics↗

N1-methylation of adenosine (m1A) 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 m1A mRNA methylation is highly discussed due to methodological differences. However, one single m1A site in mitochondrial ND5 mRNA was unanimously reported by different groups. ND5 is a subunit of complex I of the respiratory chain. It is considered essential for the coupling of oxidation and proton transport. Here we demonstrate that this m1A site might be involved in the pathophysiology of Alzheimers disease (AD). One of the pathological hallmarks of this neurodegenerative disease is mitochondrial dysfunction, mainly induced by Amyloid {beta} (A{beta}). A{beta} mainly disturbs functions of complex I and IV of the respiratory chain. However, the molecular mechanism of complex I dysfunction is still not fully understood. We found enhanced m1A methylation of ND5 mRNA in an AD cell model as well as in AD patients. Formation of this m1A methylation is catalyzed by increased TRMT10C protein levels, leading to translation repression of ND5. As a consequence, here demonstrated for the first time, TRMT10C induced m1A methylation of ND5 mRNA leads to mitochondrial dysfunction. Our findings suggest that this newly identified mechanism might be involved in A{beta}-induced mitochondrial dysfunction.

neuroscience↗