Analysis of Treacher Collins syndrome 4‐associated mutations in Schizosaccharomyces pombe

Abstract Treacher Collins syndrome (TCS) is a rare congenital disorder characterized by craniofacial deformities. Although mutations in several genes involved in ribosome biogenesis have been identified in patients with TCS, the molecular mechanisms by which these mutations exert their effects remain poorly understood. In this study, we established Schizosaccharomyces pombe models for TCS type 4 (TCS4) by introducing specific mutations in the rpa2 gene, which encodes Rpa2, the second largest subunit of RNA polymerase I (Pol I). TCS4-associated rpa2 R1022C and rpa2 R1022S mutations impaired cell growth without altering Rpa2 protein levels. These mutants were defective in 35S pre-rRNA biogenesis and were sensitive to the Pol I inhibitor BMH-21. These findings underscore the essential role of Rpa2 residues associated with TCS4 in rRNA transcription and cell growth.