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LARP3, LARP7, and MePCE are Involved in the Early Stage of Human Telomerase RNA Biogenesis

ABSTRACT: LARP3, LARP7, and MePCE are Involved in the Early Stage of Human Telomerase RNA Biogenesis

PROVIDER: PRJNA1092608 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28471776_1.fastq.gz	Fastqsanger.gz
	SRR28471776_2.fastq.gz	Fastqsanger.gz
	SRR28471777_1.fastq.gz	Fastqsanger.gz
	SRR28471777_2.fastq.gz	Fastqsanger.gz
	SRR28471778_1.fastq.gz	Fastqsanger.gz

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LARP3, LARP7, and MePCE are Involved in the Early Stage of Human Telomerase RNA Biogenesis

Project description:Human telomerase assembly is a highly dynamic process. Using biochemical approaches, we found that LARP3 and LARP7/MePCE are involved in the early stage and that their binding to hTR is destabilized when the mature hTR is produced. LARP3 plays a negative role in preventing the processing of the 3′-extended long (exL) form and binding of LARP7 and MePCE. Interestingly, the tertiary structure of the exL form prevents LARP3 binding and facilitates hTR biogenesis. Supporting this process, LARP3 at low levels promotes hTR maturation, increases telomerase activity, and elongates telomeres. LARP7 and MePCE knockdown inhibits the conversion of the 3′-extended short (exS) form into mature hTR and the cytoplasmic accumulation of hTR, resulting in telomere shortening. Our data suggest that LARP3 and LARP7/MePCE mediate the processing of hTR precursors and thus control the production of functional telomerase.

2024-07-25 | GSE262590 | GEO

A putative cap binding protein and the methyl phosphate capping enzyme Bin3/MePCE function with the Larp7 family member Pof8 in the biogenesis of telomerase

Project description:We have identified two previously uncharacterized proteins involved in telomerase biogenesis. Both proteins are required for telomerase activity and telomere length maintenance. We named these proteins Thc1 (Telomerase Holoenzyme Component 1) and Bmc1 (Bin3/MePCE 1) based on structural and sequence similarities to the nuclear cap binding complex and the methyl phosphate capping enzyme (Bin3/MePCE) in metazoans, respectively. Thc1 and Bmc1 function together with Pof8 in recognizing telomerase RNA and promoting the recruitment of the Lsm2-8 complex and the catalytic subunit to assemble functional telomerase.

2021-05-22 | GSE174822 | GEO

LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis.

Project description:Human telomerase assembly is a highly dynamic process. Using biochemical approaches, we find that LARP3 and LARP7/MePCE are involved in the early stage of human telomerase RNA (hTR) and that their binding to RNA is destabilized when the mature form is produced. LARP3 plays a negative role in preventing the processing of the 3'-extended long (exL) form and the binding of LARP7 and MePCE. Interestingly, the tertiary structure of the exL form prevents LARP3 binding and facilitates hTR biogenesis. Furthermore, low levels of LARP3 promote hTR maturation, increase telomerase activity, and elongate telomeres. LARP7 and MePCE depletion inhibits the conversion of the 3'-extended short (exS) form into mature hTR and the cytoplasmic accumulation of hTR, resulting in telomere shortening. Taken together our data suggest that LARP3 and LARP7/MePCE mediate the processing of hTR precursors and regulate the production of functional telomerase.

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A putative cap binding protein and the methyl phosphate capping enzyme Bin3/MePCE function with the Larp7 family member Pof8 in the biogenesis of telomerase

Project description:A putative cap binding protein and the methyl phosphate capping enzyme Bin3/MePCE function with the Larp7 family member Pof8 in the biogenesis of telomerase

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LARP7, a new ROS sensor, protects against heart failure by enhancing mitochondrial biogenesis

Project description:LARP7 controls the SIRT1 activity and homeostasis, which is essential for mitochondrial biogenesis, energy production and cardiac function. The deprivation of LARP7 resulted from the activation ATM pathway attenuates the mitochondrial function and biogenesis and leads to the cardiomyopathy and heart failure. Method: Heart morphology and functions were assessed by gross anatomy, serial echocardiography and histology on sections; Mitochondrial morphology and activity were evaluated by TEM and seahorse assays. The therapeutic potential of LARP7 in heart failure was evaluated in mouse myocardial infarction model either with AAV9 infection or pharmacological inhibitor.

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S. pombe Bin3 immunoprecipitation

Project description:Here we report that the methyl phosphate capping enzyme Bin3, a homolog of the human methyl phosphate capping enzyme (MePCE), is a stable component of the S. pombe telomerase complex. Bin3 associates with the telomerase complex through an interaction with the recently described LARP7 family member and telomerase component Pof8, and we demonstrate that these two factors share an evolutionarily conserved relationship in fungi.

2022-01-24 | PXD023356 | Pride

MePCE promotes Homologous Recombination through coordinating R-loop resolution at DNA Double Stranded Breaks (RNA-Seq)

Project description:MePCE is a multifunctional protein that regulates the Positive Transcription Elongation Factor b (P-TEFb) partitioning between the nucleosol and chromatin. While the role of MePCE in sequestering P-TEFb in the nucleoplasm through the 7SK ribonuclear protein complex (RNPc) is well understood, its functions on chromatin remain obscure. In order to address this gap in our knowledge, we performed mass spectrometry of MePCE interactors on chromatin. Our analysis revealed that chromatin-associated-MePCE mainly interacts with factors involved in R-loop processing and DNA repair factors. Consistent with this initial finding, MePCE is rapidly recruited to laser-mediated DNA damage and AsiSI-mediated DNA double stranded breaks (DSBs). Moreover, MePCE depletion specifically impairs DSB repair by homologous recombination (HR). To explore the molecular mechanism behind the observed HR defect, we took advantage of an inducible AsiSI system to analyze the effect of MePCE depletion in DSB repair factor recruitment and R-loop levels at over 100 genomic site-specific DSBs. Consistent with impaired HR, MePCE depletion decreases RAD51 loading and enhances R-loop levels specifically at DSBs. Analysis of R-loop protein complexes by mass spectrometry revealed that in addition to decreasing specific R-loop processing factors and chromatin remodelers, MePCE depletion increased the interaction with R-loops of the other constitutive member of the 7SK RNPc, LARP7, which is degraded by BRCA1/BARD1 upon DSB. Overall, our results uncover dynamic regulation of the 7SK RNPc at DSBs during the repair process and explain the recently observed synthetic lethality of MePCE and BRCA1 deficiency.

2025-05-23 | GSE289796 | GEO

MePCE promotes Homologous Recombination through coordinating R-loop resolution at DNA Double Stranded Breaks (ChIP-Seq)

2025-05-23 | GSE289797 | GEO

MePCE promotes Homologous Recombination through coordinating R-loop resolution at DNA Double Stranded Breaks (ChIP-Seq & DRIP-seq)

2025-05-23 | GSE261535 | GEO

LARP7, a new ROS sensor, protects against heart failure by enhancing mitochondrial biogenesis

Project description:LARP7, a new ROS sensor, protects against heart failure by enhancing mitochondrial biogenesis

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