The super elongation complex(SEC)containing positive transcription elongation factor b plays a critical role in regulating transcription elongation.AFF1 and AFF4,two members of the AF4/FMR2 family,act as central scaff...The super elongation complex(SEC)containing positive transcription elongation factor b plays a critical role in regulating transcription elongation.AFF1 and AFF4,two members of the AF4/FMR2 family,act as central scaffold proteins of SEC and are associated with various human diseases.However,their precise roles in transcriptional control remain unclear.Here,we investigate differences in the genomic distribution patterns of AFF1 and AFF4 around transcription start sites(TSSs).AFF1 mainly binds upstream of the TSS,while AFF4 is enriched downstream of the TSS.Notably,disruption of AFF4 results in slow elongation and early termination in a subset of AFF4-bound active genes,whereas AFF1 deletion leads to fast elongation and transcriptional readthrough in the same subset of genes.Additionally,AFF1 knockdown increases AFF4 levels at chromatin,and vice versa.In summary,these findings demonstrate that AFF1 and AFF4 function antagonistically to regulate RNA polymerase Ⅱ transcription.展开更多
Precise regulation of gene transcription is of great importance to development and diseases.Promoter-proximal transcriptional pause is a key and general mechanism to precisely control transcription in metazoans.Subseq...Precise regulation of gene transcription is of great importance to development and diseases.Promoter-proximal transcriptional pause is a key and general mechanism to precisely control transcription in metazoans.Subsequent to transcription initiation and synthesis of a short RNA,RNA polymerase Ⅱ(Pol Ⅱ)usually pauses at the promoter-proximal regions,standing by for further signals to be released into the productive elongation stage.Fine regulation of Pol Ⅱ pausing and release is achieved by the concerted action of many negative and positive elongation factors,including the super elongation complex(SEC).Recent studies suggested that phase-separated assemblies of transcription regulatory complexes could provide a general biophysical basis for the dynamic regulation of transcription in response to various cellular needs,though direct evidence at endogenous level in living cells is still largely lacking.Here,we summarize and discuss latest advances in understanding how phase separation contributes to RNA polymerase ll-mediated transcription,with a focus on transcriptional pause and release.展开更多
Regulation of RNA stability plays a crucial role in gene expression control.Deadenylation is the initial rate-limiting step for the majority of RNA decay events.Here,we show that RING finger protein 219(RNF219)interac...Regulation of RNA stability plays a crucial role in gene expression control.Deadenylation is the initial rate-limiting step for the majority of RNA decay events.Here,we show that RING finger protein 219(RNF219)interacts with the CCR4-NOT deadenylase complex.RNF219-CCR4-NOT exhibits deadenylation activity in vitro.RNA-seq analyses identify some of the 2-cell-specific genes and the neuronal genes significantly downregulated upon RNF219 knockdown,while upregulated after depletion of the CCR4-NOT subunit CNOTIO in mouse embryonic stem(ES)cells.RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation.Our study suggests that RNF219 is a novel interacting partner of CCR4-NOT and required for maintenance of ES cell pluripotency.展开更多
基金supported by grants from the National Key R&D Program of China(2018YFA0800100 to C.L.,2018YFA0800103 to Z.L.)the National Natural Science Foundation of China(32030017 and 31970617 to C.L.,31970626 to Z.L.)Shenzhen Science and Technology Program(JCYJ20210324133602008 to C.L.,JCYJ20210324133601005 to Z.L.).
文摘The super elongation complex(SEC)containing positive transcription elongation factor b plays a critical role in regulating transcription elongation.AFF1 and AFF4,two members of the AF4/FMR2 family,act as central scaffold proteins of SEC and are associated with various human diseases.However,their precise roles in transcriptional control remain unclear.Here,we investigate differences in the genomic distribution patterns of AFF1 and AFF4 around transcription start sites(TSSs).AFF1 mainly binds upstream of the TSS,while AFF4 is enriched downstream of the TSS.Notably,disruption of AFF4 results in slow elongation and early termination in a subset of AFF4-bound active genes,whereas AFF1 deletion leads to fast elongation and transcriptional readthrough in the same subset of genes.Additionally,AFF1 knockdown increases AFF4 levels at chromatin,and vice versa.In summary,these findings demonstrate that AFF1 and AFF4 function antagonistically to regulate RNA polymerase Ⅱ transcription.
基金supported by grants from the National Key R&D Program of China (2018YFA0800100 and 2018YFA0800101 to CL2018YFA0800103 to Z.L.)+1 种基金the National Natural Science Foundation of China (32030017 and 31970626 to C.L31970617 to Z.L.)。
文摘Precise regulation of gene transcription is of great importance to development and diseases.Promoter-proximal transcriptional pause is a key and general mechanism to precisely control transcription in metazoans.Subsequent to transcription initiation and synthesis of a short RNA,RNA polymerase Ⅱ(Pol Ⅱ)usually pauses at the promoter-proximal regions,standing by for further signals to be released into the productive elongation stage.Fine regulation of Pol Ⅱ pausing and release is achieved by the concerted action of many negative and positive elongation factors,including the super elongation complex(SEC).Recent studies suggested that phase-separated assemblies of transcription regulatory complexes could provide a general biophysical basis for the dynamic regulation of transcription in response to various cellular needs,though direct evidence at endogenous level in living cells is still largely lacking.Here,we summarize and discuss latest advances in understanding how phase separation contributes to RNA polymerase ll-mediated transcription,with a focus on transcriptional pause and release.
基金Studies in this manuscript were supported by funds provided by the National Natural Science Foundation of China(31671343 and 31970617 to C.L.,31970626 to Z.L.,31700718 to D.H.)National Key R&D Program of China(2018YFA0800100 to C.L.)+2 种基金Natural Science Foundation of Jiangsu Province of China(BK20170020 to Z.L.,BK20170663 to D.H.)China Postdoctoral Science Foundation(2018M630492 to D.H.)Scientific Research Foundation of the Graduate School of Southeast University(YBPY1888 to Y.W.).
文摘Regulation of RNA stability plays a crucial role in gene expression control.Deadenylation is the initial rate-limiting step for the majority of RNA decay events.Here,we show that RING finger protein 219(RNF219)interacts with the CCR4-NOT deadenylase complex.RNF219-CCR4-NOT exhibits deadenylation activity in vitro.RNA-seq analyses identify some of the 2-cell-specific genes and the neuronal genes significantly downregulated upon RNF219 knockdown,while upregulated after depletion of the CCR4-NOT subunit CNOTIO in mouse embryonic stem(ES)cells.RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation.Our study suggests that RNF219 is a novel interacting partner of CCR4-NOT and required for maintenance of ES cell pluripotency.
