Impaired binding affinity of YTHDC1 with METTL3/METTL14 results in R-loop accumulation in myelodysplastic neoplasms with DDX41 mutation DOI Creative Commons
Hongtae Kim, Won Chan Hwang, Kibeom Park

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Сен. 20, 2023

Abstract DEAD box helicase 41 (DDX41) mutations are the most prevalent predisposition to familial myelodysplastic syndrome (MDS). However, precise roles of these variants in pathogenesis MDS have yet be elucidated. Here, we discovered a novel mechanism by which DDX41 contributes R-loop-induced DNA damage responses (DDR) cooperation with m6A-METTL complex (MAC) and YTHDC1 usingDDX41knockout (KO) andDDX41knock-in (KI, R525H, Y259C) cell lines as well primary samples from patients. Compared wild type (WT),DDX41KO KI led increased levels m6A RNA methylated R-loop damage. Interestingly, found that regulates m6A/R-loop interacting MAC components. Further, promoted recruitment R-loops promoting binding between METTL3 YTHDC1, was dysregulated inDDX41-deficient cells. Collectively, demonstrated plays key role physiological control YTHDC1. These findings provide insights into how defects influence suggest potential therapeutic targets for treatment MDS.

Язык: Английский

RNA modification in normal hematopoiesis and hematologic malignancies DOI Creative Commons
Xi Chen,

Yixiao Yuan,

Fan Zhou

и другие.

MedComm, Год журнала: 2024, Номер 5(11)

Опубликована: Окт. 23, 2024

Abstract N6‐methyladenosine (m6A) is the most abundant RNA modification in eukaryotic cells. Previous studies have shown that m6A plays a critical role under both normal physiological and pathological conditions. Hematopoiesis differentiation are highly regulated processes, recent on mRNA methylation revealed how this controls cell fate malignant hematopoietic states. However, despite these insights, comprehensive understanding of its complex roles between development diseases remains elusive. This review first provides an overview components biological functions regulators. Additionally, it highlights origin, process, characteristics, regulatory mechanisms stem cells, as well features, immune properties, self‐renewal pathways leukemia Last, article systematically reviews latest research advancements factors hematopoiesis related diseases. More importantly, explores targeting regulators various signaling could effectively intervene leukemia, providing new insights potential therapeutic targets. Targeting may hold promise for achieving more precise effective treatments.

Язык: Английский

Процитировано

0
RNA methylation: where to from here for hematological malignancies? DOI
Andrew A. Guirguis

Experimental Hematology, Год журнала: 2024, Номер 143, С. 104694 - 104694

Опубликована: Дек. 6, 2024

Язык: Английский

Процитировано

0
Splice epitranscriptomics and DNA damage repair together: ALKBH5-m6A-SF3B1 regulation in leukemic transformation DOI Creative Commons
Zhongyu Zou, Chuan He

Molecular Cell, Год журнала: 2023, Номер 83(7), С. 1022 - 1023

Опубликована: Апрель 1, 2023

Язык: Английский

Процитировано

0
Impaired binding affinity of YTHDC1 with METTL3/METTL14 results in R-loop accumulation in myelodysplastic neoplasms with DDX41 mutation DOI Creative Commons
Hongtae Kim, Won Chan Hwang, Kibeom Park

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Сен. 20, 2023

Abstract DEAD box helicase 41 (DDX41) mutations are the most prevalent predisposition to familial myelodysplastic syndrome (MDS). However, precise roles of these variants in pathogenesis MDS have yet be elucidated. Here, we discovered a novel mechanism by which DDX41 contributes R-loop-induced DNA damage responses (DDR) cooperation with m6A-METTL complex (MAC) and YTHDC1 usingDDX41knockout (KO) andDDX41knock-in (KI, R525H, Y259C) cell lines as well primary samples from patients. Compared wild type (WT),DDX41KO KI led increased levels m6A RNA methylated R-loop damage. Interestingly, found that regulates m6A/R-loop interacting MAC components. Further, promoted recruitment R-loops promoting binding between METTL3 YTHDC1, was dysregulated inDDX41-deficient cells. Collectively, demonstrated plays key role physiological control YTHDC1. These findings provide insights into how defects influence suggest potential therapeutic targets for treatment MDS.

Язык: Английский

Процитировано

0