The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences are usually folded into secondary“knot”st...The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences 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.展开更多
Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a v...Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we deleted Dhx36 in advanced germ cells with Stra8-GFPCre and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 plays crucial roles in late stages of spermatogenesis.展开更多
基金National Key Research and Development Program of ChinaGrant/Award Number:2019YFA0801601+1 种基金National Natural Science Foundation of ChinaGrant/Award Number:31930029,91854111 and 31571490。
文摘The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences 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.
基金supported by grants from the National Key R&D Program of China(2021YFC2700200 and 2022YFC2702602)the National Natural Science Foundation of China(31930034)the Science and Technology Commission of Shanghai Municipality(19JC1415800 to M.-H.T.).
文摘Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we deleted Dhx36 in advanced germ cells with Stra8-GFPCre and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 plays crucial roles in late stages of spermatogenesis.
