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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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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

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.

| S-EPMC11250828 | biostudies-literature

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

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.

2020-08-14 | GSE155898 | GEO

Role of LARP7 in meiotic sex chromosome silencing

Project description:Meiotic sex chromosome inactivation (MSCI) is an essential event in meiotic progression in mammalian spermatogenesis. We found that La Ribonucleoprotein 7 (LARP7) is involved in MSCI. LARP7 plays a role in fetal germ cells to promote their proliferation, but is once abolished in postnatal gonocytes and re-expresses in spermatocytes at the onset of meiosis. In spermatocytes, LARP7 localizes to the XY body, a compartmentalized chromatin domain on sex chromosomes. This study aimed to elucidate a possible function of LARP7 in the XY body by using germline-specific Larp7-deficient mice.

2024-10-01 | GSE261526 | 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: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

| PRJNA731852 | ENA

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

| PRJNA655954 | ENA

Identification of small RNAs interacting with LARP7

Project description:The La-related protein LARP7 has been mainly described as a component of the 7SK small nuclear ribonucleoprotein (snRNP) complex, which negatively regulates RNA polymerase II by sequestering the positive transcription elongation factor b (P-TEFb). In our studies, we discovered a novel, 7SK snRNP-independent function of LARP7. We show that LARP7 interacts with the U6 spliceosomal RNA as well as with the small nucleolar RNAs (snoRNAs) directing the 2'-O-methylations of U6. Importantly, in the absence of LARP7, significantly less 2'-O-methylations are deposited on U6 affecting splicing fidelity. Mutations in the LARP7 gene have been associated with the Alazami syndrome, a form of primordial dwarfism characterized by intellectual disability. We describe a novel loss-of-function mutation of LARP7 occurring in Alazami patients and detect reduced 2'-O-methylations of U6 in patient-derived samples. Thus, aberrant posttranscriptional RNA modifications of the spliceosomal U6 snRNA may contribute to the development of this severe disease.

2020-02-03 | GSE126592 | GEO

Identify RNAs That are Bound by LARP7

Project description:Anti-LARP7 RNA immunoprecipitation (RIP) coupled with RNA-seq assays showed significant enrichment of U6 snRNA, but not other 4 spliceosomal snRNAs, in LARP7 complexes in adult mouse testis.

2019-11-07 | GSE128831 | GEO

LARP7 suppresses endothelial-to-mesenchymal transition by coupling with TRIM28

Project description:LARP7 plays a pivotal role in regulating endothelial-to-mesenchymal transition(EndMT) and EndMT-associated heart valve formation. LARP7 directly interactes with TRIM28 and cooperatively represses SLUG transcription, which thereby suppresses EndMT of endothelial cells. More importantly, inducible knockout of LARP7 or TRIM28 in the endocardium promotes EndMT in vivo and leads to the valvular hyperplasia.

2023-09-22 | GSE165400 | GEO

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