Abstract RECQ5 is a member of the RECQ helicase family that maintains genomic stability. However, the molecular mechanism of RECQ5 in this biological process remains elusive. Here, we show that RECQ5 localizes in the dense fibrillar component of nucleolus and associates with several pre-rRNA processing factors. It recognizes pre-rRNA and is able to unwind double-stranded RNA in vitro. Loss of RECQ5 induces the accumulation of 47S, 30SL5′, and 30S pre-rRNA, and the reduction of 21S pre-rRNA, suggesting that it regulates the processing of pre-rRNA. Cancer-associated mutations of RECQ5 abolish its nucleolar localization as well as its helicase activities. Moreover, lacking RECQ5 leads to the unprocessed pre-rRNA hybridizing with rDNA, triggering the R-loop formation and ATR activation. Since both RECQ5 and ATR protect genomic stability in nucleolus, suppression of RECQ5 sensitizes tumor cells to the ATR inhibitor treatment. Collectively, this study reveals that RECQ5 plays a crucial role in pre-rRNA processing and ribosomal DNA (rDNA) stability.
Ma et al. (Fri,) studied this question.