Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells
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ABSTRACT:
PROVIDER: PRJNA930709 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26164752_1.fastq.gz | Fastqsanger.gz | |||
| SRR26164752_2.fastq.gz | Fastqsanger.gz | |||
| SRR26164753_1.fastq.gz | Fastqsanger.gz | |||
| SRR26164753_2.fastq.gz | Fastqsanger.gz | |||
| SRR26164754_1.fastq.gz | Fastqsanger.gz |
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Project description:Two RNA binding proteins, UPF1 and LIN28A, have well-known functions in posttranscriptional regulations and stem cell differentiation. Most studies on UPF1 and LIN28A have focused on the molecular mechanism in differentiated cells and stem cell differentiation, respectively. We revealed that LIN28A directly interacts with UPF1, which happens before UPF1 forms a complex with UPF2, thereby resulting in the reduction of UPF1 phosphorylation and inhibition of nonsense-mediated mRNA decay (NMD). Our studies reveal that cell fate is determined by transcriptome regulation through UPF1-LIN28A interaction in hPSCs.
2023-12-12 | GSE224358 | GEO
Project description:UPF1 and LIN28A are RNA-binding proteins involved in post-transcriptional regulation and stem cell differentiation. Most studies on UPF1 and LIN28A have focused on the molecular mechanisms of differentiated cells and stem cell differentiation, respectively. We reveal that LIN28A directly interacts with UPF1 before UPF1-UPF2 complexing, thereby reducing UPF1 phosphorylation and inhibiting nonsense-mediated mRNA decay (NMD). We identify the interacting domains of UPF1 and LIN28A; moreover, we develop a peptide that impairs UPF1-LIN28A interaction and augments NMD efficiency. Transcriptome analysis of human pluripotent stem cells (hPSCs) confirms that the levels of NMD targets are significantly regulated by both UPF1 and LIN28A. Inhibiting the UPF1-LIN28A interaction using a CPP-conjugated peptide promotes spontaneous differentiation by repressing the pluripotency of hPSCs during proliferation. Furthermore, the UPF1-LIN28A interaction specifically regulates transcripts involved in ectodermal differentiation. Our study reveals that transcriptome regulation via the UPF1-LIN28A interaction in hPSCs determines cell fate.
| S-EPMC10762078 | biostudies-literature
Project description:A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in microRNA biogenesis, diverse molecular roles have been recognized. In the nervous system, LIN28A is known to play critical roles in proliferation and differentiation of neural progenitor cells (NPC). We profiled the endogenous LIN28A-interacting proteins in NPC differentiated from human induced pluripotent stem (iPS) cells using immunoprecipitation and liquid chromatography-tandem mass spectrometry. We identified over 500 LIN28A-interacting proteins, including 156 RNA-independent interactors. Functions of these proteins span a wide range of gene regulatory processes. Our analysis opens multiple avenues for elaborating molecular roles and characteristics of LIN28A.
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Project description:The RNA binding protein LIN28A is a stem- and progenitor marker and one of the factors necessary to induce pluripotent stem cells in vitro. LIN28A has been shown to promote the proliferative capacity of neural progenitor cells but its specific role during embryonal and postnatal brain development still remains widely unknown. A high and characteristic overexpression of LIN28A has been identified in malignant brain tumors called embryonal tumors with multilayered rosettes (ETMR). Radial glia cells of the ventricular zone are proposed as a cell of origin for those tumors.
2022-02-15 | PXD028044 | Pride
Project description:LIN28A, an RNA-binding protein, plays an important role in porcine induced pluripotent stem cells (piPSCs). However, the molecular mechanism of LIN28A maintaining pluripotency in piPSCs remains unclear. The aim of this study was to explore the functions of LIN28A in piPSCs. Here we explored the functions of LIN28A in piPSCs by overexpressing and knocking down LIN28A. We performed total RNA sequencing (RNA-seq) on piPSCs and the expression levels of relevant-genes were detected by qRT-PCR, western blot and immunofluorescence staining. The proliferation ability of piPSCs was related to the expression level of LIN28A and the proliferation ability decreased when LIN28A was knocked down. When the expression level of LIN28A was lower than 20% compared with the negative control (shNC) group, the pluripotency of piPSCs would disappear and differentiate to the neuroectoderm. We also found that LIN28A inhibited the expression levels of DUSP (dual-specificity phosphatases) family phosphatases and then activated mitogen-activated protein kinases (MAPK) signaling pathway. This work revealed that LIN28A activated MAPK signaling pathway to maintain the pluripotency and proliferation ability of piPSCs. Our results provided a new resource for exploring the functions of LIN28A in piPSCs.
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Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, Lin28 was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28A preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells. Examination of RNA binding of LIN28A and translation in mouse embryonic stem cell.
2012-10-25 | E-GEOD-37111 | biostudies-arrayexpress
Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, LIN28A was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28 preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells. Examination of miRNA level in embryonic stem cell treated with siRNA for GFP or for Lin28a
2012-10-25 | E-GEOD-37112 | biostudies-arrayexpress
Project description:LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, LIN28A was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28 preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells. Examination of mRNA level in embryonic stem cell treated with siRNA for GFP or for Lin28a
2012-10-25 | E-GEOD-37113 | biostudies-arrayexpress
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