Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA.

Fungal pathogens threaten ecosystems and human health. Understanding the molecular basis of their virulence is key to develop new treatment strategies. Here, we characterize NCS2*, a point mutation identified in a clinical baker's yeast isolate.

E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation.

Post-translational modifications by ubiquitin-like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin-related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP) and is linked to the noncanonical E1 enzyme Uba4 (ubiquitin-like protein activator 4). While Urm1 has also been observed to conjugate to target proteins like other UBLs, the molecular mechanism of its attachment remains unknown.

Analysis of codon-specific translation by ribosome profiling.

Chemical modifications of RNA molecules can affect translation in multiple ways. Therefore, it is critical to understand how their absence changes cellular translation dynamics and in particular codon-specific translation. In this chapter, we discuss the application of ribosome profiling to analyze changes in codon-specific translation and differential translation in Saccharomyces cerevisiae and human cells.

METTL15 interacts with the assembly intermediate of murine mitochondrial small ribosomal subunit to form m4C840 12S rRNA residue.

Mammalian mitochondrial ribosomes contain a set of modified nucleotides, which is distinct from that of the cytosolic ribosomes. Nucleotide m4C840 of the murine mitochondrial 12S rRNA is equivalent to the dimethylated m4Cm1402 residue of Escherichia coli 16S rRNA. Here we demonstrate that mouse METTL15 protein is responsible for the formation of m4C residue of the 12S rRNA.

Mouse Trmt2B protein is a dual specific mitochondrial metyltransferase responsible for mU formation in both tRNA and rRNA.

RNA molecules of all species contain modified nucleotides and particularly mU residues. The vertebrate mitochondrial small subunit rRNA contains mU nucleotide in a unique site. In this work we found an enzyme, TRMT2B, responsible for the formation of this nucleotide and mU residues in a number of mitochondrial tRNA species.

Skewed X-inactivation is common in the general female population.

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance.