CstF-64 supports pluripotency and regulates cell cycle progression in embryonic stem cells through histone 3' end processing.
Bottom Line: Similarly, the role of 3' end processing in regulation of ESC pluripotency and cell cycle is poorly understood.However, τCstF-64 only partially compensates for lost CstF-64 function, despite being recruited to the histone mRNA 3' end-processing complex.Reduction of τCstF-64 in CstF-64-deficient ESCs results in even greater levels of histone mRNA polyadenylation, suggesting that both CstF-64 and τCstF-64 function to inhibit polyadenylation of histone mRNAs.
Affiliation: Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430-6540, USA.Show MeSH
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Mentions: We found that CstF-64 interacts more strongly with symplekin than does τCstF-64 (Figure 6D) (24). Others have shown that the CstF-64/symplekin interaction is essential to link FLASH and Lsm11 with the other CPSF factors in the histone mRNA 3′ end-processing complex (15,18). Based on these data, we propose a model in which interaction of CstF-64 with symplekin inhibits the polyadenylation of replication-dependent histone mRNAs in wild type ESCs, supporting both pluripotency and progression through the histone cell cycle checkpoint into S phase while suppressing differentiation. Our data also demonstrate a stronger recruitment of certain CPSF and CstF factors to the replication-dependent histone mRNA 3′ end processing complex in the absence of CstF-64, including CPSF-100, CPSF-160 and CstF-77 (Figure 6A). The increased recruitment of these factors in the Cstf2E6 cells could result in a U7 snRNP complex that favors polyadenylation of histone mRNAs instead of the usual histone stem loop processing (Figure 7).
Affiliation: Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430-6540, USA.