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Single molecule nanoscopy reveals that nuclear myosin VI regulates the spatial organization of mammalian transcription initiation

ABSTRACT: Single molecule nanoscopy reveals that nuclear myosin VI regulates the spatial organization of mammalian transcription initiation

PROVIDER: PRJNA628703 | ENA |

REPOSITORIES: ENA

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Single molecule nanoscopy reveals that nuclear myosin VI regulates the spatial organization of mammalian transcription initiation

Project description:During transcription, RNA Polymerase II (RNAPII) is spatially organised into clusters that correlate with transcription activity. However, the assembly, organisation and stability of these transcription units remains unknown. Here, we have combined single molecule imaging with genomics approaches in order to explore the role of nuclear myosin VI in the nanoscale organisation of RNAPII. We can reveal that myosin VI acts as the molecular anchor that holds RNAPII into these transcription factories. Perturbation of myosin VI leads to the disruption of RNAPII localisation, changes in chromatin organisation and subsequently a decrease in gene expression. This role of Myosin VI is particularly important for transcription events following stimulation, where multiple genes are simultaneously activated.

2020-05-31 | GSE149448 | GEO

Nuclear myosin VI maintains replication fork stability

Project description:The actin cytoskeleton is of fundamental importance for cellular structure and plasticity. However, abundance and function of filamentous (F-) actin in the nucleus are still controversial. Here we show that the actin-based molecular motor myosin VI contributes to the stabilization of stalled or reversed replication forks. In response to DNA replication stress, myosin VI associates with stalled replication intermediates and cooperates with the AAA ATPase WRNIP1 in protecting these structures from DNA2-mediated nucleolytic attack. Using functionalized DARPins to manipulate myosin VI levels in a compartment-specific manner, we provide evidence for the direct involvement of myosin VI in the nucleus and against a contribution of the abundant cytoplasmic pool during the replication stress response.

2023-05-04 | PXD035394 | Pride

Study of endogenous interactome of Myosin VI

Project description:Immunoprecipitation of endogenous Myosin VI in Human Cell Lines (Caco-2, HeLa, MCF10A, MDA-MB-231) and identification of true interactors by mass spectrometry

2021-07-08 | PXD026697 | Pride

How Myosin VI Traps its Off-State, is Activated and Dimerizes

Project description:Myosin VI (Myo6) is the only minus-end directed nanomotor on actin, allowing it to uniquely contribute to numerous cellular functions. As for other nanomotors, proper functioning of Myo6 relies on precise spatio-temporal control of motor activity via a poorly defined off-state and interactions with partners. Our structural, functional, and cellular studies reveal key features of myosin regulation and indicate that not all partners can activate Myo6. TOM1 and Dab2 cannot bind the off-state while, GIPC1 binds Myo6, releases its auto-inhibition and triggers proximal dimerization. Myo6 partners thus differentially recruit Myo6. We solved a crystal structure of the proximal dimerization domain, and show that its disruption compromises endocytosis in HeLa cells, emphasizing the importance of Myo6 dimerization. Finally, we show that the L926Q deafness mutation disrupts Myo6 auto-inhibition and indirectly impairs proximal dimerization. Our study thus demonstrates the importance of partners in the control of Myo6 auto-inhibition, localization, and activation.

2024-01-26 | PXD044767 | Pride

Porcine myosin-VI: characterization of a new mammalian unconventional myosin.

Project description: Not available

| S-EPMC2120210 | biostudies-other

Ribonucleoprotein immunoprecipitation of myosin proteins and myosin-specific chaperones in fission yeast

Project description:Ribonucleoprotein immunoprecipitation microarray (RIp-chip) study using various myosin proteins and myosin-specific chaperones from the fission Schizosaccaromyces pombe

2010-03-01 | E-TABM-335 | biostudies-arrayexpress

Myo6 regulate transcriptional pause release

Project description:Global run-on sequencing analyses of murine T cells with or without Myosin VI were performed to determine the effect of anti-CD3 stimulation and loss of Myosin VI on the transcription elongation

2015-01-28 | E-MTAB-2381 | biostudies-arrayexpress

Myosin PTM peptide mapping from hibernating and active bears and squirrels

Project description:Recent discoveries in the field of skeletal muscle have found that the contractile protein myosin is able to dictate the resting metabolic rate of this organ. In this study we aimed to investigate if myosin is involved in the process of metabolic shutdown which is observed during hibernation. Comparing large and small hibernating mammals, we found that in small hibernating mammals, the rate of ATP turnover dictated by myosin was altered and that this was also dependent upon the temperature of skeletal muscle. We further investigated changes to the whole proteome of these animals and observed that in small hibernators found significant changes to sarcomere organization during hibernating periods. Finally, we identified hyperphosphorylation upon the myosin molecule in these small hibernators which was predicted to induce stability changes to this molecule. In this dataset, we performed PTM peptide mapping of the myosin protein derived from skeletal muscle fibre samples from squirrels collected in summer and winter time.

2024-04-29 | PXD044685 | Pride

Ribonucleoprotein immunoprecipitation of fission yeast to study myosin proteins and myosin-specific chaperones

Project description:Ribonucleoprotein immunoprecipitation microarray (RIp-chip) study using various myosin proteins and myosin-specific chaperones from the fission Schizosaccaromyces pombe. Two strains were used. In rng3TAP the rng3 protein has been tagged with TAP to allow its detection and immunoprecipitation. The TAP strain expresses the TAP sequence alone (without being attached to an other protein)

2008-12-23 | E-TABM-516 | biostudies-arrayexpress

Myosin VI deafness mutation prevents the initiation of processive runs on actin.

Project description: Not available

| S-EPMC4371908 | biostudies-literature