To unwind the biological knots: The DNA/RNA G-quadruplex resolvase RHAU (DHX36) in development and disease

The G-quadruplex (G4) sequences are short fragments of 4-interval triple guanine (G) with frequent and ubiquitous distribution in the genome and RNA transcripts. The G4 sequences are usually folded into secondary knot structure via Hoogsteen hydrogen bond to exert negative regulation on a variety of biological processes, including DNA replication and transcription, mRNA translation, and telomere maintenance. Recent structural biological and mouse genetics studies have demonstrated that RHAU (DHX36) can bind and unwind the G4 knots to modulate embryonic development and postnatal organ function. Deficiency of RHAU gives rise to embryonic lethality, impaired organogenesis, and organ dysfunction. These studies uncovered the pivotal G4 resolvase function of RHAU to release the G4 barrier, which plays fundamental roles in development and physiological homeostasis. This review discusses the latest advancements and findings in deciphering RHAU functions using animal models.

Automated summary

The G-quadruplex (G4) sequences, short fragments consisting of multiple guanine (G) nucleotides, are widely distributed in the genome and RNA transcripts. Recent studies have shown that RHAU can bind and unwind the G4 structures, regulating embryonic development and organ function. Deficiency of RHAU leads to embryonic lethality and organ dysfunction. These studies reveal the crucial role of RHAU in development and physiological homeostasis.