NELFE

更新于：2025-05-07

基本信息

别名

D6S45、negative elongation factor complex member E、Negative elongation factor E

+ [6]

简介

Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (PubMed:10199401, PubMed:27256882). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (PubMed:11940650, PubMed:12612062, PubMed:27256882). Provides the strongest RNA binding activity of the NELF complex and may initially recruit the NELF complex to RNA (PubMed:18303858, PubMed:27256882, PubMed:27282391). (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II.

关联

100 项与 NELFE 相关的临床结果

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100 项与 NELFE 相关的转化医学

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0 项与 NELFE 相关的专利（医药）

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项与 NELFE 相关的文献（医药）

2025-04-15·The FASEB Journal

CAF‐derived exosomal LINC01711 promotes breast cancer progression by activating the miR‐4510/NELFE axis and enhancing glycolysis

Article

作者: Zhu, Hong ; Wu, Chunxia ; Gao, Yali ; Li, Jinping ; Tao, Shuang ; Zhang, Yi ; Wang, Xiang

AbstractBreast cancer (BRCA) is among the most prevalent malignancies in women, characterized by a complex tumor microenvironment significantly influenced by cancer‐associated fibroblasts (CAFs). CAFs contribute to tumor progression by secreting exosomes that can modulate cancer cell behavior. This study highlights how CAF‐derived exosomes transmit the long non‐coding RNA (lncRNA) LINC01711, which activates TXN through the miR‐4510/NELFE axis, thereby enhancing glycolysis in BRCA cells. Utilizing BRCA single‐cell sequencing data from the GEO database, the study employed dimensionality reduction, clustering, and cell annotation techniques to uncover the central role of NELFE in BRCA. Experimental findings revealed that LINC01711 is highly expressed in CAF‐derived exosomes, which upregulate TXN via the miR‐4510/NELFE axis, promoting the glycolytic pathway and subsequently increasing the proliferation, migration, and invasion potential of BRCA cells. These results shed light on a novel molecular mechanism underlying BRCA progression and suggest potential targets for therapeutic intervention.

2025-03-07·Science Advances

Structural insights into promoter-proximal pausing of RNA polymerase II at +1 nucleosome

Article

作者: Naganuma, Masahiro ; Henmi, Masami ; Kurumizaka, Hitoshi ; Uejima, Tamami ; Sekine, Shun-ichi ; Miyamoto-Kohno, Sayako ; Aoki, Mari ; Goto, Mie ; Shirouzu, Mikako ; Ehara, Haruhiko ; Kujirai, Tomoya ; Ito, Tomoko

The metazoan transcription elongation complex (EC) of RNA polymerase II (RNAPII) generally stalls between the transcription start site and the first (+1) nucleosome. This promoter-proximal pausing involves negative elongation factor (NELF), 5,6-dichloro-1-β- d -ribobenzimidazole sensitivity-inducing factor (DSIF), and transcription elongation factor IIS (TFIIS) and is critical for subsequent productive transcription elongation. However, the detailed pausing mechanism and the involvement of the +1 nucleosome remain enigmatic. Here, we report cryo–electron microscopy structures of ECs stalled on nucleosomal DNA. In the absence of TFIIS, the EC is backtracked/arrested due to conflicts between NELF and the nucleosome. We identified two alternative binding modes of NELF, one of which reveals a critical contact with the downstream DNA through the conserved NELF-E basic helix. Upon binding with TFIIS, the EC progressed to the nucleosome to establish a paused EC with a partially unwrapped nucleosome. This paused EC strongly restricts EC progression further downstream. These structures illuminate the mechanism of RNAPII pausing/stalling at the +1 nucleosome.

2025-01-01·Journal of Psychiatric Research

Enhancing genetic discovery through narrow phenotyping in schizophrenia

Article

作者: Bruttan, Maria ; Skvortsova, Veronika ; Makarov, Valentin ; Mamchur, Aleksandra ; Pavlova, Olga ; Morozova, Anna ; Shingaliev, Andrey ; Keskinov, Anton ; Kashtanova, Daria ; Matkava, Lorena ; Astafieva, Vasilisa ; Yudin, Sergey ; Kraevoy, Sergey ; Pavlov, Konstantin ; Nebogina, Kira ; Ivanov, Mikhail ; Yudin, Vladimir ; Mitrofanov, Sergey ; Nekrasova, Aleksandra ; Yakovchik, Anna ; Nekrasov, Aleksander ; Zelenova, Elena ; Terekhov, Mikhail ; Kozlov, Aleksander

BACKGROUNDSchizophrenia varies greatly from person to person, mainly because of its polygenic nature. Consequently, schizophrenia patients form distinct subphenotypes of schizophrenia, with specific symptom patterns and outcomes.METHODSThis study included 4257 adults, with long-term schizophrenia (control - 8955 individuals) who were assessed for schizophrenia with potentially severe outcomes based on following criteria: disability in functional and/or physical domains before the age of 40; severe negative symptoms (present in infancy or shortly after onset); a continuous course of the disease. Additionally, the time of the onset and aggressive/antisocial tendencies were assessed as one the predictors of potentially severe outcomes. A total of 817 participants met at least three of these criteria, i.e., had disruptive schizophrenia. A genome-wide and transcriptome-wide association study was conducted using linear regression and the PrediXcan algorithm. The obtained data were used to develop a polygenic risk model for early risk prediction of schizophrenia with potentially severe outcomes.RESULTSSignificant associations were found between schizophrenia and variants in CAMTA1, TRHDE, NELFE, and others. The PRS model demonstrated high performance in training, internal and external validation (ROC AUC of 0.9, 0.89, and 0.68, respectively). The functional pathway analysis highlighted pathways involved in ATP metabolism, myeloid cell differentiation, and apoptotic processes.CONCLUSIONSubphenotyping schizophrenia may enhance the discovery of genetic factors affecting its development and progression. The GWAS and TWAS findings revealed general mechanisms involved in the development of schizophrenia with potentially severe outcomes, such as synapse regulation, inflammation, and apoptosis.

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