Work

A dual-activity Topoisomerase Complex Regulates both Transcription and Translation

Year: 2021

Type: preprint

Abstract: Topoisomerases solve topological problems for DNA, but whether they function similarly for RNA remains unclear. Here we show that the Topoisomerase 3b (TOP3B)-TDRD3 complex acts on both DNA and RNA. On DNA, TOP3B-TDRD3 binds transcription start or termination regions; and inactivation of TOP3B topoisomerase activity decreases expression of some though not all genes downregulated in TOP3B-KO and TDRD3-KO cells. On mRNA, TOP3B-TDRD3 preferentially binds coding regions of long mRNAs and stabilizes them independently of TOP3B topoisomerase activity. Moreover, ablation of the complex or inactivation of TOP3B catalytic activity alters translation for some mRNAs, suggesting that TOP3B-TDRD3 may solve RNA topological problems. Finally, several schizophrenia and autism-risk genes are bound and regulated by TOP3B-TDRD3 at either transcription or translation. Our data suggest that TOP3B-TDRD3 can regulate transcription and translation by topoisomerase activity dependent or independent mechanisms; and disruption of either function could contribute to pathogenesis of psychiatric disorders in TOP3B mutation carriers.

Source: Research Square

DOI: 10.21203/rs.3.rs-1054387/v1