title: CstF-64 supports pluripotency and regulates cell cycle progression in embryonic stem cells through histone 3' end processing.
abstract: Embryonic stem cells (ESCs) exhibit a unique cell cycle with a shortened G1 phase that supports their pluripotency, while apparently buffering them against pro-differentiation stimuli. In ESCs, expression of replication-dependent histones is a main component of this abbreviated G1 phase, although the details of this mechanism are not well understood. Similarly, the role of 3' end processing in regulation of ESC pluripotency and cell cycle is poorly understood. To better understand these processes, we examined mouse ESCs that lack the 3' end-processing factor CstF-64. These ESCs display slower growth, loss of pluripotency and a lengthened G1 phase, correlating with increased polyadenylation of histone mRNAs. Interestingly, these ESCs also express the τCstF-64 paralog of CstF-64. 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. These results suggest that CstF-64 plays a key role in modulating the cell cycle in ESCs while simultaneously controlling histone mRNA 3' end processing.
authors: Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430-6540, USA.
authors: Bradford A
authors: BA
authors: Youngblood
authors: Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430-6540, USA.
authors: Petar N
authors: PN
authors: Grozdanov
authors: Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430-6540, USA clint.macdonald@ttuhsc.edu.
authors: Clinton C
authors: CC
authors: MacDonald
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D039241:Cleavage Stimulation Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D039904:Pluripotent Stem Cells / Q000378:metabolism; D026721:RNA 3' End Processing; D020885:Ribonucleoprotein, U7 Small Nuclear / Q000737:chemistry / Q000378:metabolism
chemical_list: D039241:Cleavage Stimulation Factor; C492658:Cstf2t protein, mouse; D006657:Histones; D020885:Ribonucleoprotein, U7 Small Nuclear