Roles of the Ultra‑Conserved Ribosomal RNA Methyltransferase KsgA in Ribosome Biogenesis
Jason P. Rife
KsgA is a ribosomal RNA methyltransferase that modifies two adjacent adenosines in the small subunit. It was originally identified by virtue of the fact that its absence in several bacteria provides resistance to the antibiotic kasugamycin. The ksgA gene appears to be ubiquitously spread throughout all phylogenies, thus suggesting that it was part of the last universal common ancestor. Despite common origins many present‑day orthologs of KsgA perform unrelated secondary functions. Examples include KsgA orthologs in eukarotic organisms, termed Dim1, that play an essential role in the processome complex in ribosome biogenesis and mt‑TFB, a nuclear encoded enzyme that functions in mitochondria as a transcription factor and a KsgA‑like methyltransferase. KsgA itself plays a larger role in ribosome biogenesis in Escherichia coli beyond that of a methyltransferase; it is a critical factor in the late stages of 30S assembly. A strong evolutionary relationship is seen between KsgA and the antibiotic resistance enzyme Erm. While Erm and KsgA act on separate substrates, they show remarkable structural similarity and catalyze essentially the same reaction. Despite nearly 40 years of investigation recent reports of KsgA describe fundamental aspects of substrate binding and function and illustrate that many questions remain to be answered.