Biology subjects

Brümmer, A.

Publications and source records attributed to Brümmer, A..

3 recordsLinked to original sources

bioRxiv2025

The 18S rRNA methyltransferase, BUD23, is required for appropriate lipid and mitochondrial metabolism

Efficient energy metabolism is essential for health and its dysregulation drives cardiometabolic disease. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features - including short 5 UTR length and GC-rich post-initiation codon usage - characteristic of mitochondrial and lipogenic proteins. Genetic analyses and Mendelian randomisation support a role for BUD23 in human cardiometabolic traits and disease burden. Together, our findings uncover a conserved translational control mechanism that regulates energy state, from cellular metabolism through to human cardiometabolic health.

cell biology↗

bioRxiv2023

Disentangling genetic effects on transcriptional and post-transcriptional gene regulation through integrating exon and intron expression QTLs

Expression quantitative trait loci (eQTL) studies typically consider exon expression of genes and discard intronic RNA sequencing reads despite their information on RNA metabolism. Here, we quantified genetic effects on exon and intron levels of genes and their ratio in lymphoblastoid cell lines, revealing thousands of cis-QTLs of each type. Genetic effects were often shared between cis-QTL types, but 6084 (41%) were not detectable at exon levels. We show that exon levels preferentially capture genetic effects on transcriptional regulation, while exon-intron-ratios better detect those on co- and post-transcriptional processes. Considering all cis-QTL types substantially increased the number of colocalizing GWAS variants (by 61%). It further allowed dissecting the potential gene regulatory processes underlying GWAS associations, suggesting comparable contributions by transcriptional (48%) and co- and post-transcriptional regulation (42%) to complex traits. Overall, integrating intronic RNA sequencing reads in eQTL studies expands our understanding of genetic effects on gene regulatory processes.

genomics↗

bioRxiv2019

LincRNA sequences are biased to counteract their translation

Long intergenic non-coding RNAs (lincRNAs) represent a large fraction of transcribed loci in eukaryotic genomes. Although classified as non-coding, most lincRNAs contain open reading frames (ORFs), and it remains unclear why cytoplasmic lincRNAs are not or very inefficiently translated. Here, we analysed signatures of repressed translation in lincRNA sequences from six eukaryotes. In species under stronger selection, i.e. fission yeast and worm, we detected significantly shorter ORFs than in intronic and non-transcribed control regions, a suboptimal sequence context around start codons for translation initiation, and trinucleotides ("codons") corresponding to less abundant tRNAs than codons in control regions, potentially impeding translation elongation. We verified that varying tRNA expression levels affect ribosome-binding to lincRNAs by analyzing data from five human cell lines. Notably, for three cell lines, codons in abundant cytoplasmic lincRNAs corresponded to lower expressed tRNAs than control codons, substantiating cell type-specific repression of lincRNA translation in human. Finally, comparing non-coding with peptide-encoding ORFs suggested that codon usage at the start of ORFs to be of particular relevance for ribosome-binding. The identified sequence signatures may assist distinguishing peptide- from real non-coding lincRNAs in a cell.

genomics↗