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Professor Sushma Grellscheid's Outputs (29)

Deciphering the impact of PROM1 alternative splicing on human photoreceptor development and maturation. (2024)
Journal Article
Moya-Molina, M., Dorgau, B., Flood, E., Letteboer, S. J. F., Lorentzen, E., Coxhead, J., Smith, G., Roepman, R., Nagaraja Grellscheid, S., Armstrong, L., & Lako, M. (2024). Deciphering the impact of PROM1 alternative splicing on human photoreceptor development and maturation. Cell Death and Disease, 15(10), Article 721. https://doi.org/10.1038/s41419-024-07105-7

Alternative splicing (AS) is a crucial mechanism contributing to proteomic diversity, which is highly regulated in tissue- and development-specific patterns. Retinal tissue exhibits one of the highest levels of AS. In particular, photoreceptors have... Read More about Deciphering the impact of PROM1 alternative splicing on human photoreceptor development and maturation..

PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects. (2024)
Journal Article
Atkinson, R., Georgiou, M., Yang, C., Szymanska, K., Lahat, A., Vasconcelos, E. J. R., …Lako, M. (2024). PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects. Nature Communications, 15(1), Article 3138. https://doi.org/10.1038/s41467-024-47253-0

The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient indu... Read More about PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects..

A bending rigidity parameter for stress granule condensates (2023)
Journal Article
Law, J. O., Jones, C. M., Stevenson, T., Williamson, T. A., Turner, M. S., Kusumaatmaja, H., & Grellscheid, S. N. (2023). A bending rigidity parameter for stress granule condensates. Science Advances, 9(20), https://doi.org/10.1126/sciadv.adg0432

Interfacial tension plays an important role in governing the dynamics of droplet coalescence and determining how condensates interact with and deform lipid membranes and biological filaments. We demonstrate that an interfacial tension-only model is i... Read More about A bending rigidity parameter for stress granule condensates.

MERISTEM-DEFECTIVE regulates the balance between stemness and differentiation in the root meristem through RNA splicing control (2023)
Journal Article
Thompson, H., Shen, W., Matus, R., Kakkar, M., Jones, C., Dolan, D., Grellscheid, S., Yang, X., Zhang, N., Mozaffari-Jovin, S., Chen, C., Zhang, X., Topping, J., & Lindsey, K. (2023). MERISTEM-DEFECTIVE regulates the balance between stemness and differentiation in the root meristem through RNA splicing control. Development, 150(7), Article dev201476. https://doi.org/10.1242/dev.201476

Plants respond to environmental stresses through controlled stem cell maintenance and meristem activity. One level of gene regulation is RNA alternative splicing. However, the mechanistic link between stress, meristem function and RNA splicing is poo... Read More about MERISTEM-DEFECTIVE regulates the balance between stemness and differentiation in the root meristem through RNA splicing control.

Peptide‐Based Coacervate‐Core Vesicles with Semipermeable Membranes (2022)
Journal Article
Abbas, M., Law, J. O., Grellscheid, S. N., Huck, W. T., & Spruijt, E. (2022). Peptide‐Based Coacervate‐Core Vesicles with Semipermeable Membranes. Advanced Materials, 34(34), Article 2202913. https://doi.org/10.1002/adma.202202913

Coacervates droplets have long been considered as potential protocells to mimic living cells. However, these droplets lack a membrane and are prone to coalescence, limiting their ability to survive, interact, and organize into higher-order assemblies... Read More about Peptide‐Based Coacervate‐Core Vesicles with Semipermeable Membranes.

Particle detection and tracking with DNA (2022)
Journal Article
O’Hare, C. A., Matsos, V. G., Newton, J., Smith, K., Hochstetter, J., Jaiswar, R., Kyaw, W., McNamara, A., Kuncic, Z., Grellscheid, S. N., & Bœhm, C. (2022). Particle detection and tracking with DNA. The European Physical Journal C, 82(4), Article 306. https://doi.org/10.1140/epjc/s10052-022-10264-6

We present the first proof-of-concept simulations of detectors using biomaterials to detect particle interactions. The essential idea behind a “DNA detector” involves the attachment of a forest of precisely-sequenced single or double-stranded nucleic... Read More about Particle detection and tracking with DNA.

Deep conservation of ribosome stall sites across RNA processing genes (2021)
Journal Article
Chyżyńska, K., Labun, K., Jones, C., Grellscheid, S. N., & Valen, E. (2021). Deep conservation of ribosome stall sites across RNA processing genes. NAR Genomics and Bioinformatics, 3(2), https://doi.org/10.1093/nargab/lqab038

The rate of translation can vary depending on the mRNA template. During the elongation phase the ribosome can transiently pause or permanently stall. A pause can provide the nascent protein with the time to fold or be transported, while stalling can... Read More about Deep conservation of ribosome stall sites across RNA processing genes.

Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner (2021)
Journal Article
Lagnado, A., Leslie, J., Ruchaud‐Sparagano, M., Victorelli, S., Hirsova, P., Ogrodnik, M., Collins, A. L., Vizioli, M. G., Habiballa, L., Saretzki, G., Evans, S. A., Salmonowicz, H., Hruby, A., Geh, D., Pavelko, K. D., Dolan, D., Reeves, H. L., Grellscheid, S., Wilson, C. H., Pandanaboyana, S., …Passos, J. F. (2021). Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner. The EMBO Journal, 40(9), Article e106048. https://doi.org/10.15252/embj.2020106048

Cellular senescence is characterized by an irreversible cell cycle arrest as well as a pro-inflammatory phenotype, thought to contribute to aging and age-related diseases. Neutrophils have essential roles in inflammatory responses; however, in certai... Read More about Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner.

Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation (2020)
Journal Article
Vietri, M., Schultz, S. W., Bellanger, A., Jones, C. M., Petersen, L. I., Raiborg, C., Skarpen, E., Pedurupillay, C. R. J., Kjos, I., Kip, E., Timmer, R., Jain, A., Collas, P., Knorr, R. L., Grellscheid, S. N., Kusumaatmaja, H., Brech, A., Micci, F., Stenmark, H., & Campsteijn, C. (2020). Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation. Nature Cell Biology, 22(7), 856-867. https://doi.org/10.1038/s41556-020-0537-5

The ESCRT-III membrane fission machinery maintains the integrity of the nuclear envelope. Although primary nuclei resealing takes minutes, micronuclear envelope ruptures seem to be irreversible. Instead, micronuclear ruptures result in catastrophic m... Read More about Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation.

An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning (2019)
Journal Article
Ehrmann, I., Crichton, J. H., Gazzara, M. R., James, K., Liu, Y., Grellscheid, S. N., …Elliott, D. J. (2019). An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning. eLife, 8, Article e39304. https://doi.org/10.7554/elife.39304

Male germ cells of all placental mammals express an ancient nuclear RNA binding protein of unknown function called RBMXL2. Here we find that deletion of the retrogene encoding RBMXL2 blocks spermatogenesis. Transcriptome analyses of age-matched delet... Read More about An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning.

An integrated transcriptional analysis of the developing human retina (2019)
Journal Article
Mellough, C. B., Bauer, R., Collin, J., Dorgau, B., Zerti, D., Dolan, D. W., …Lako, M. (2019). An integrated transcriptional analysis of the developing human retina. Development, 146(2), Article dev169474. https://doi.org/10.1242/dev.169474

The scarcity of embryonic/foetal material as a resource for direct study means that there is still limited understanding of human retina development. Here, we present an integrated transcriptome analysis combined with immunohistochemistry in human ey... Read More about An integrated transcriptional analysis of the developing human retina.

The bystander effect contributes to the accumulation of senescent cells in vivo (2018)
Journal Article
da Silva, P. F., Ogrodnik, M., Kucheryavenko, O., Glibert, J., Miwa, S., Cameron, K., Ishaq, A., Saretzki, G., Nagaraja-Grellscheid, S., Nelson, G., & von Zglinicki, T. (2019). The bystander effect contributes to the accumulation of senescent cells in vivo. Aging Cell, 18(1), Article e12848. https://doi.org/10.1111/acel.12848

Senescent cells accumulate with age in multiple tissues and may cause age‐associated disease and functional decline. In vitro, senescent cells induce senescence in bystander cells. To see how important this bystander effect may be for accumulation of... Read More about The bystander effect contributes to the accumulation of senescent cells in vivo.

Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa (2018)
Journal Article
Buskin, A., Zhu, L., Chichagova, V., Basu, B., Mozaffari-Jovin, S., Dolan, D., Droop, A., Collin, J., Bronstein, R., Mehrotra, S., Farkas, M., Hilgen, G., White, K., Pan, K.-T., Treumann, A., Hallam, D., Bialas, K., Chung, G., Mellough, C., Ding, Y., …Lako, M. (2018). Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nature Communications, 9(1), Article 4234. https://doi.org/10.1038/s41467-018-06448-y

Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause non-syndromic retinal disease. Here, we generate transcriptome profiles from RP... Read More about Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa.

Medicinal Mascarene Aloe s: An audit of their phytotherapeutic potential (2017)
Journal Article
Lobine, D., Cummins, I., Govinden-Soulange, J., Ranghoo-Sanmukhiya, M., Lindsey, K., Chazot, P., …Howes, M. (2018). Medicinal Mascarene Aloe s: An audit of their phytotherapeutic potential. Fitoterapia, 124, 120-126. https://doi.org/10.1016/j.fitote.2017.10.010

A phytochemical and biological investigation of the endemic Mascarene Aloes (Aloe spp.), including A. tormentorii (Marais) L.E.Newton & G.D.Rowley, A. purpurea Lam, A. macra Haw., A. lomatophylloides Balf.f and A. vera (synonym A. barbadensis Mill.),... Read More about Medicinal Mascarene Aloe s: An audit of their phytotherapeutic potential.

Cellular senescence drives age-dependent hepatic steatosis (2017)
Journal Article
Ogrodnik, M., Miwa, S., Tchkonia, T., Tiniakos, D., Wilson, C. L., Lahat, A., …Jurk, D. (2017). Cellular senescence drives age-dependent hepatic steatosis. Nature Communications, 8, https://doi.org/10.1038/ncomms15691

The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent c... Read More about Cellular senescence drives age-dependent hepatic steatosis.

Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68 (2016)
Journal Article
Feracci, M., Foot, J. N., Grellscheid, S. N., Danilenko, M., Stehle, R., Gonchar, O., …Dominguez, C. (2016). Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68. Nature Communications, 7, Article 10355. https://doi.org/10.1038/ncomms10355

Sam68 and T-STAR are members of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins. T-STAR is a tissue-specific paralogue th... Read More about Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68.

A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities (2015)
Journal Article
Ghosh, P., Grellscheid, S. N., & Sowdhamini, R. (2016). A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities. Journal of Biomolecular Structure and Dynamics, 34(9), 1979-1986. https://doi.org/10.1080/07391102.2015.1100551

The Transformer2 (Tra2) proteins in humans are homologues of the Drosophila Tra2 protein. One of the two RNA-binding paralogs, Tra2β, has been very well-studied over the past decade, but not much is known about Tra2α. It was very recently shown that... Read More about A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities.

Comparison of senescence-associated miRNAs in primary skin and lung fibroblasts (2015)
Journal Article
Holly, A., Grellscheid, S., van de Walle, P., Dolan, D., Pilling, L., Daniels, D., von Zglinicki, T., Ferrucci, L., Melzer, D., & Harries, L. (2015). Comparison of senescence-associated miRNAs in primary skin and lung fibroblasts. Biogerontology, 16, 423–434. https://doi.org/10.1007/s10522-015-9560-5

MicroRNAs are non-coding RNAs with roles in many cellular processes. Tissue-specific miRNA profiles associated with senescence have been described for several cell and tissue types. We aimed to characterise miRNAs involved in core, rather than tissue... Read More about Comparison of senescence-associated miRNAs in primary skin and lung fibroblasts.

Detecting translational regulation by change point analysis of ribosome profiling data sets (2014)
Journal Article
Zupanic, A., Meplan, C., Grellscheid, S., Mathers, J., Kirkwood, T., Hesketh, J., & Shanley, D. (2014). Detecting translational regulation by change point analysis of ribosome profiling data sets. RNA, 20(10), 1507-1518. https://doi.org/10.1261/rna.045286.114

Ribo-Seq maps the location of translating ribosomes on mature mRNA transcripts. While during normal translation, ribosomedensity is constant along the length of the mRNA coding region, this can be altered in response to translational regulatoryevents... Read More about Detecting translational regulation by change point analysis of ribosome profiling data sets.