19 research outputs found
YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators.
The N6-methyladenosine (m6A) modification regulates mRNA stability and translation. Here, we show that transcriptomic m6A modification can be dynamic and the m6A reader protein YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) promotes mRNA decay during cell cycle. Depletion of YTHDF2 in HeLa cells leads to the delay of mitotic entry due to overaccumulation of negative regulators of cell cycle such as Wee1-like protein kinase (WEE1). We demonstrate that WEE1 transcripts contain m6A modification, which promotes their decay through YTHDF2. Moreover, we found that YTHDF2 protein stability is dependent on cyclin-dependent kinase 1 (CDK1) activity. Thus, CDK1, YTHDF2, and WEE1 form a feedforward regulatory loop to promote mitotic entry. We further identified Cullin 1 (CUL1), Cullin 4A (CUL4A), damaged DNA-binding protein 1 (DDB1), and S-phase kinase-associated protein 2 (SKP2) as components of E3 ubiquitin ligase complexes that mediate YTHDF2 proteolysis. Our study provides insights into how cell cycle mediators modulate transcriptomic m6A modification, which in turn regulates the cell cycle
Ni- and Pd-Catalyzed Synthesis of Substituted and Functionalized Allylic Boronates
Two highly efficient and convenient methods for the synthesis of functionalized and substituted allylic boronates are described. In one procedure, readily available allylic acetates are converted to allylic boronates catalyzed by Ni/PCy<sub>3</sub> or Ni/PPh<sub>3</sub> complexes with high levels of stereoselectivity and in good yields. Alternatively, the borylation can be accomplished with commercially available Pd catalysts [e.g., Pd<sub>2</sub>(dba)<sub>3</sub>, PdCl<sub>2</sub>, Pd/C], starting with easily accessed allylic halides
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YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators
The N6-methyladenosine (m6A) modification regulates mRNA stability and translation. Here, we show that transcriptomic m6A modification can be dynamic and the m6A reader protein YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) promotes mRNA decay during cell cycle. Depletion of YTHDF2 in HeLa cells leads to the delay of mitotic entry due to overaccumulation of negative regulators of cell cycle such as Wee1-like protein kinase (WEE1). We demonstrate that WEE1 transcripts contain m6A modification, which promotes their decay through YTHDF2. Moreover, we found that YTHDF2 protein stability is dependent on cyclin-dependent kinase 1 (CDK1) activity. Thus, CDK1, YTHDF2, and WEE1 form a feedforward regulatory loop to promote mitotic entry. We further identified Cullin 1 (CUL1), Cullin 4A (CUL4A), damaged DNA-binding protein 1 (DDB1), and S-phase kinase-associated protein 2 (SKP2) as components of E3 ubiquitin ligase complexes that mediate YTHDF2 proteolysis. Our study provides insights into how cell cycle mediators modulate transcriptomic m6A modification, which in turn regulates the cell cycle
A Catalytic Enantioselective Tandem Allylation Strategy for Rapid Terpene Construction: Application to the Synthesis of Pumilaside Aglycon
Catalytic enantioselective 1,2-diboration of 1,3-dienes
followed
by cascade allylborations with dicarbonyls provides rapid entry into
carbocyclic reaction products. The stereochemical course of this reaction
was studied along with its application in the synthesis of <i>pumilaside</i> aglycon
A Catalytic Enantioselective Tandem Allylation Strategy for Rapid Terpene Construction: Application to the Synthesis of Pumilaside Aglycon
Catalytic enantioselective 1,2-diboration of 1,3-dienes
followed
by cascade allylborations with dicarbonyls provides rapid entry into
carbocyclic reaction products. The stereochemical course of this reaction
was studied along with its application in the synthesis of <i>pumilaside</i> aglycon
A Catalytic Enantioselective Tandem Allylation Strategy for Rapid Terpene Construction: Application to the Synthesis of Pumilaside Aglycon
Catalytic enantioselective 1,2-diboration of 1,3-dienes
followed
by cascade allylborations with dicarbonyls provides rapid entry into
carbocyclic reaction products. The stereochemical course of this reaction
was studied along with its application in the synthesis of <i>pumilaside</i> aglycon
A Catalytic Enantioselective Tandem Allylation Strategy for Rapid Terpene Construction: Application to the Synthesis of Pumilaside Aglycon
Catalytic enantioselective 1,2-diboration of 1,3-dienes
followed
by cascade allylborations with dicarbonyls provides rapid entry into
carbocyclic reaction products. The stereochemical course of this reaction
was studied along with its application in the synthesis of <i>pumilaside</i> aglycon
A Catalytic Enantioselective Tandem Allylation Strategy for Rapid Terpene Construction: Application to the Synthesis of Pumilaside Aglycon
Catalytic enantioselective 1,2-diboration of 1,3-dienes
followed
by cascade allylborations with dicarbonyls provides rapid entry into
carbocyclic reaction products. The stereochemical course of this reaction
was studied along with its application in the synthesis of <i>pumilaside</i> aglycon
A Catalytic Enantioselective Tandem Allylation Strategy for Rapid Terpene Construction: Application to the Synthesis of Pumilaside Aglycon
Catalytic enantioselective 1,2-diboration of 1,3-dienes
followed
by cascade allylborations with dicarbonyls provides rapid entry into
carbocyclic reaction products. The stereochemical course of this reaction
was studied along with its application in the synthesis of <i>pumilaside</i> aglycon