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1. CDK9 inhibition constrains multiple oncogenic transcriptional and epigenetic pathways in prostate cancer

Author

Rahman, Razia, Rahaman, Muhammed H., Hanson, Adrienne R., Choo, Nicholas, Xie, Jianling, Townley, Scott L., Shrestha, Raj, Hassankhani, Ramin, Islam, Saiful, Ramm, Susanne, Simpson, Kaylene J., Risbridger, Gail P., Best, Giles, Centenera, Margaret M., Balk, Steven P., Kichenadasse, Ganessan, Taylor, Renea A., Butler, Lisa M., Tilley, Wayne D., Conn, Simon J., Lawrence, Mitchell G., Wang, Shudong, and Selth, Luke A.

Published
2024
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4. Author Correction: CDK9 inhibition constrains multiple oncogenic transcriptional and epigenetic pathways in prostate cancer

Author

Rahman, Razia, Rahaman, Muhammed H., Hanson, Adrienne R., Choo, Nicholas, Xie, Jianling, Townley, Scott L., Shrestha, Raj, Hassankhani, Ramin, Islam, Saiful, Ramm, Susanne, Simpson, Kaylene J., Risbridger, Gail P., Best, Giles, Centenera, Margaret M., Balk, Steven P., Kichenadasse, Ganessan, Taylor, Renea A., Butler, Lisa M., Tilley, Wayne D., Conn, Simon J., Lawrence, Mitchell G., Wang, Shudong, and Selth, Luke A.

Published
2024
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6. Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes

Author

Mielczarek, Olga, Rogers, Carolyn H., Zhan, Yinxiu, Matheson, Louise S., Stubbington, Michael J.T., Schoenfelder, Stefan, Bolland, Daniel J., Javierre, Biola M., Wingett, Steven W., Várnai, Csilla, Segonds-Pichon, Anne, Conn, Simon J., Krueger, Felix, Andrews, Simon, Fraser, Peter, Giorgetti, Luca, and Corcoran, Anne E.

Published
2023
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7. Circular RNAs drive oncogenic chromosomal translocations within the MLL recombinome in leukemia

Author

Conn, Vanessa M., Gabryelska, Marta, Toubia, John, Kirk, Kirsty, Gantley, Laura, Powell, Jason A., Cildir, Gökhan, Marri, Shashikanth, Liu, Ryan, Stringer, Brett W., Townley, Scott, Webb, Stuart T., Lin, He, Samaraweera, Saumya E., Bailey, Sheree, Moore, Andrew S., Maybury, Mellissa, Liu, Dawei, Colella, Alex D., Chataway, Timothy, Wallington-Gates, Craig T., Walters, Lucie, Sibbons, Jane, Selth, Luke A., Tergaonkar, Vinay, D’Andrea, Richard J., Pitson, Stuart M., Goodall, Gregory J., and Conn, Simon J.

Published
2023
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8. The Non-Coding RNA Journal Club: Highlights on Recent Papers-7.

Author

Xiao, Hua, Shiu, Patrick KT, Gabryleska, Marta, Conn, Simon J, Dey, Abhishek, Chakrabarti, Kausik, Regouc, Manuel, Pichler, Martin, Ørom, Ulf Andersson Vang, Santulli, Gaetano, Nishiwada, Satoshi, Goel, Ajay, Nagarajan, Vaishnavi, Timmons, Lisa, Alahari, Suresh K, Laprovitera, Noemi, Ferracin, Manuela, Hu, Po, and Jin, Hailing

Abstract

We are delighted to share with you our seventh Journal Club and highlight some of the most interesting papers published recently [...].

Published
2019

9. CDK9 inhibition inhibits multiple oncogenic transcriptional and epigenetic pathways in prostate cancer.

Author

Rahman, Razia, Rahaman, Muhammed H., Hanson, Adrienne R., Choo, Nicholas, Xie, Jianling, Townley, Scott L., Shrestha, Raj, Hassankhani, Ramin, Islam, Saiful, Ramm, Susanne, Simpson, Kaylene J., Risbridger, Gail P., Best, Giles, Centenera, Margaret M., Balk, Steven P., Kichenadasse, Ganessan, Taylor, Renea A., Butler, Lisa M., Tilley, Wayne D., and Conn, Simon J.

Abstract

Background: Cyclin-dependent kinase 9 (CDK9) stimulates oncogenic transcriptional pathways in cancer and CDK9 inhibitors have emerged as promising therapeutic candidates. Methods: The activity of an orally bioavailable CDK9 inhibitor, CDKI-73, was evaluated in prostate cancer cell lines, a xenograft mouse model, and patient-derived tumor explants and organoids. Expression of CDK9 was evaluated in clinical specimens by mining public datasets and immunohistochemistry. Effects of CDKI-73 on prostate cancer cells were determined by cell-based assays, molecular profiling and transcriptomic/epigenomic approaches. Results: CDKI-73 inhibited proliferation and enhanced cell death in diverse in vitro and in vivo models of androgen receptor (AR)-driven and AR-independent models. Mechanistically, CDKI-73-mediated inhibition of RNA polymerase II serine 2 phosphorylation resulted in reduced expression of BCL-2 anti-apoptotic factors and transcriptional defects. Transcriptomic and epigenomic approaches revealed that CDKI-73 suppressed signaling pathways regulated by AR, MYC, and BRD4, key drivers of dysregulated transcription in prostate cancer, and reprogrammed cancer-associated super-enhancers. These latter findings prompted the evaluation of CDKI-73 with the BRD4 inhibitor AZD5153, a combination that was synergistic in patient-derived organoids and in vivo. Conclusion: Our work demonstrates that CDK9 inhibition disrupts multiple oncogenic pathways and positions CDKI-73 as a promising therapeutic agent for prostate cancer, particularly aggressive, therapy-resistant subtypes. [ABSTRACT FROM AUTHOR]

Published
2024
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10. CircRNAs in Plants

Author

Lai, Xuelei, Bazin, Jérémie, Webb, Stuart, Crespi, Martin, Zubieta, Chloe, Conn, Simon J., COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, Rezaei, Nima, Series Editor, and Xiao, Junjie, editor

Published
2018
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11. A Neuroethics Framework for the Australian Brain Initiative

Author

Carter, Adrian, Richards, Linda J., Apthorp, Deborah, Azghadi, Mostafa Rahimi, Badcock, David R., Balleine, Bernard, Bekkers, John M., Berk, Michael, Bourne, James A., Bradley, Andrew P., Breakspear, Michael, Brichta, Alan, Carter, Olivia, Castles, Anne, Chakli, Khaled, Cohen-Woods, Sarah, Conn, Simon J., Cornish, Jennifer, Cornish, Kim, de Zubicaray, Greg, Egan, Gary F., Enticott, Peter G., Fitzgibbon, Bernadette M., Forlini, Cynthia, Fornito, Alex, Griffiths, Lyn, Gullifer, Judith, Hall, Wayne, Halliday, Glenda, Hannan, Anthony J., Harrer, Stefan, Harvey, Alan, Hatherly, Chris, Hickie, Ian B., Kennett, Jeanette, Kiernan, Matthew, Kilpatrick, Trevor, Kiral-Kornek, Isabell, Korgaonkar, Mayuresh S., Lawrence, Andrew J., Leventer, Rick, Levy, Neil, Licinio, Julio, Lovell, Nigel, Mackellar, Geoff, Malcolm, Lynne, Mason, Alice, Mattingley, Jason B., Medland, Sarah E., Michie, Patricia T., Nithianantharajah, Jess, Parker, John, Payne, Jonathan M., Poole-Warren, Laura, Sah, Pankaj, Sarnyai, Zoltan, Schofield, Peter R., Shimoni, Olga, Shum, David H.K., Silk, Tim, Slee, Mark, Smith, Ashleigh E., Soulis, Tina, Sriram, Sharath, Stuart, Greg J., Tapson, Jonathan, Thompson, Matthew B., van Schaik, André, Vincent, Nicole A., Vissel, Bryce, and Waters, Allison

Published
2019
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12. ESRP1 controls biogenesis and function of a large abundant multiexon circRNA

Author

Liu, Dawei, primary, Dredge, B Kate, additional, Bert, Andrew G, additional, Pillman, Katherine A, additional, Toubia, John, additional, Guo, Wenting, additional, Dyakov, Boris J A, additional, Migault, Melodie M, additional, Conn, Vanessa M, additional, Conn, Simon J, additional, Gregory, Philip A, additional, Gingras, Anne-Claude, additional, Patel, Dinshaw, additional, Wu, Baixing, additional, and Goodall, Gregory J, additional

Published
2023
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16. Calcium Compartmentation in Arabidopsis Mesophyll Cells, A Mechanism to Regulate Apoplastic Calcium, Photosynthetic Rates and Growth, Involves Low-affinity, High-capacity Ca2+/H+ Antiporters

Author

Conn, Simon J, Gilliham, Matthew, Tyerman, Stephen, Kaiser, Brent, and Leigh, Roger

Subjects
Calcium, Arabidopsis, SiCSA, Photosynthesis, Homeostasis
Abstract

The way calcium (Ca) is stored in plants impacts upon plant, human and animal nutrition. An X-ray microanalysis study of over 40 angiosperm species has highlighted conserved accumulation patterns for Ca across different plant families; Ca is often stored in specific leaf cell-types. For instance, in grass monocots Ca accumulation occurs within vacuoles of epidermal cells whereas in the majority of eudicots Ca is predominantly stored within mesophyll cell vacuoles. To correlate gene expression with Ca accumulation profiles we micropipetted RNA from epidermal and mesophyll cells of the eudicot Arabidopsis thaliana. Cell specific RNA libraries were analysed by microarray and qPCR revealing a number of candidate membrane transporters with greater relative expression in the Ca-rich mesophyll. Knockout mutagenesis of one candidate AtCAX1, a tonoplast-localized Ca2+/H+-antiporter, resulted in no mutant phenotype. When the expression of AtCAX3, a complementing family member was also abolished, this resulted in a reduction in total leaf [Ca] and perturbance of the Ca distribution pattern. The double knockout plant had a 3-fold higher apoplastic [Ca] which correlated with reduced stomatal conductance, photosynthetic rate and consequently growth. Apoplastic [Ca], stomatal conductance and growth rate could be recovered to wild-type levels by reducing [Ca] in the growth medium. We implicate CAX1 and its homologues as major regulators of Ca distribution and apoplastic [Ca] in leaves within and between plant orders. Such information will be helpful for the manipulation of Ca within specific cell types of leafy vegetables as a tool for improving human and animal nutrition.

Published
2009

18. Functional Characterisation of the Circular RNA, circHTT(2-6), in Huntington’s Disease

Author

Gantley, Laura, primary, Stringer, Brett W., additional, Conn, Vanessa M., additional, Ootsuka, Youichirou, additional, Holds, Duncan, additional, Slee, Mark, additional, Aliakbari, Kamelya, additional, Kirk, Kirsty, additional, Ormsby, Rebecca J., additional, Webb, Stuart T., additional, Hanson, Adrienne, additional, Lin, He, additional, Selth, Luke A., additional, and Conn, Simon J., additional

Published
2023
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19. The Non-Coding RNA Journal Club: Highlights on Recent Papers—12

Author

Shiu, Patrick K. T., primary, Ilieva, Mirolyuba, additional, Holm, Anja, additional, Uchida, Shizuka, additional, DiStefano, Johanna K., additional, Bronisz, Agnieszka, additional, Yang, Ling, additional, Asahi, Yoh, additional, Goel, Ajay, additional, Yang, Liuqing, additional, Nuthanakanti, Ashok, additional, Serganov, Alexander, additional, Alahari, Suresh K., additional, Lin, Chunru, additional, Pardini, Barbara, additional, Naccarati, Alessio, additional, Jin, Jing, additional, Armanios, Beshoy, additional, Zhong, Xiao-bo, additional, Sideris, Nikolaos, additional, Bayraktar, Salih, additional, Castellano, Leandro, additional, Gerber, André P., additional, Lin, He, additional, Conn, Simon J., additional, Sleem, Doha Magdy Mostafa, additional, and Timmons, Lisa, additional

Published
2023
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21. Use of synthetic circular RNA spike-ins (SynCRS) for normalization of circular RNA sequencing data

Author

Conn, Vanessa M., Liu, Ryan, Gabryelska, Marta, and Conn, Simon J.

Abstract

High-throughput RNA sequencing enables the quantification of transcript abundance and the identification of novel transcripts in biological samples. These include circular RNAs (circRNAs), a family of alternatively spliced RNA molecules that form a continuous loop. However, quantification and comparison of circRNAs between RNA sequencing libraries remain challenging due to confounding errors introduced during exonuclease digestion, library preparation and RNA sequencing itself. Here we describe a set of synthetic circRNA spike-ins—termed ‘SynCRS’—that can be added directly to purified RNA samples before exonuclease digestion and library preparation. SynCRS, introduced either individually or in combinations of varying size and abundance, can be integrated into all next-generation sequencing workflows and, critically, facilitate the quantitative calibration of circRNA transcript abundance between samples, tissue types, species and laboratories. Our step-by-step protocol details the generation of SynCRS and guides users on the stoichiometry of SynCRS spike-in to RNA samples, followed by the bioinformatic steps required to facilitate quantitative comparisons of circRNAs between libraries. The laboratory steps to produce the SynCRS require an additional 3 d on top of the high throughput circRNA sequencing and bioinformatics. The protocol is suitable for users with basic experience in molecular biology and bioinformatics.

Published
2024
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26. miR‐200/375 control epithelial plasticity‐associated alternative splicing by repressing the RNA‐binding protein Quaking

Author

Pillman, Katherine A, Phillips, Caroline A, Roslan, Suraya, Toubia, John, Dredge, B Kate, Bert, Andrew G, Lumb, Rachael, Neumann, Daniel P, Li, Xiaochun, Conn, Simon J, Liu, Dawei, Bracken, Cameron P, Lawrence, David M, Stylianou, Nataly, Schreiber, Andreas W, Tilley, Wayne D, Hollier, Brett G, Khew‐Goodall, Yeesim, Selth, Luke A, Goodall, Gregory J, and Gregory, Philip A

Published
2018
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31. Erratum: A Neuroethics Framework for the Australian Brain Initiative (Neuron (2019) 101(3) (365–369), (S0896627319300054), (10.1016/j.neuron.2019.01.004))

Author

Carter, Adrian, Richards, Linda J., Apthorp, Deborah, Azghadi, Mostafa Rahimi, Badcock, David R., Balleine, Bernard, Bekkers, John M., Berk, Michael, Bourne, James A., Bradley, Andrew P., Breakspear, Michael, Brichta, Alan, Carter, Olivia, Castles, Anne, Chakli, Khaled, Cohen-Woods, Sarah, Conn, Simon J., Cornish, Jennifer, Cornish, Kim, de Zubicaray, Greg, Egan, Gary F., Enticott, Peter G., Fitzgibbon, Bernadette M., Forlini, Cynthia, Fornito, Alex, Griffiths, Lyn, Gullifer, Judith, Hall, Wayne, Halliday, Glenda, Hannan, Anthony J., Harrer, Stefan, Harvey, Alan, Hatherly, Chris, Hickie, Ian B., Kennett, Jeanette, Kiernan, Matthew, Kilpatrick, Trevor, Kiral-Kornek, Isabell, Korgaonkar, Mayuresh S., Lawrence, Andrew J., Leventer, Rick, Levy, Neil, Licinio, Julio, Lovell, Nigel, Mackellar, Geoff, Malcolm, Lynne, Mason, Alice, Mattingley, Jason B., Medland, Sarah E., Michie, Patricia T., Nithianantharajah, Jess, Parker, John, Payne, Jonathan M., Poole-Warren, Laura, Sah, Pankaj, Sarnyai, Zoltan, Schofield, Peter R., Shimoni, Olga, Shum, David H.K., Silk, Tim, Slee, Mark, Smith, Ashleigh E., Soulis, Tina, Sriram, Sharath, Stuart, Greg J., Tapson, Jonathan, Thompson, Matthew B., van Schaik, André, Vincent, Nicole A., Vissel, Bryce, Waters, Allison, other, and, Carter, Adrian, Richards, Linda J., Apthorp, Deborah, Azghadi, Mostafa Rahimi, Badcock, David R., Balleine, Bernard, Bekkers, John M., Berk, Michael, Bourne, James A., Bradley, Andrew P., Breakspear, Michael, Brichta, Alan, Carter, Olivia, Castles, Anne, Chakli, Khaled, Cohen-Woods, Sarah, Conn, Simon J., Cornish, Jennifer, Cornish, Kim, de Zubicaray, Greg, Egan, Gary F., Enticott, Peter G., Fitzgibbon, Bernadette M., Forlini, Cynthia, Fornito, Alex, Griffiths, Lyn, Gullifer, Judith, Hall, Wayne, Halliday, Glenda, Hannan, Anthony J., Harrer, Stefan, Harvey, Alan, Hatherly, Chris, Hickie, Ian B., Kennett, Jeanette, Kiernan, Matthew, Kilpatrick, Trevor, Kiral-Kornek, Isabell, Korgaonkar, Mayuresh S., Lawrence, Andrew J., Leventer, Rick, Levy, Neil, Licinio, Julio, Lovell, Nigel, Mackellar, Geoff, Malcolm, Lynne, Mason, Alice, Mattingley, Jason B., Medland, Sarah E., Michie, Patricia T., Nithianantharajah, Jess, Parker, John, Payne, Jonathan M., Poole-Warren, Laura, Sah, Pankaj, Sarnyai, Zoltan, Schofield, Peter R., Shimoni, Olga, Shum, David H.K., Silk, Tim, Slee, Mark, Smith, Ashleigh E., Soulis, Tina, Sriram, Sharath, Stuart, Greg J., Tapson, Jonathan, Thompson, Matthew B., van Schaik, André, Vincent, Nicole A., Vissel, Bryce, Waters, Allison, and other, and

Abstract

(Neuron 101, 365–369; February 6, 2019) In the original publication of this NeuroView, the member list for the Australian Brain Alliance was omitted. This has now been corrected online. Neuron apologizes for the error.

Published
2020

36. A Neuroethics Framework for the Australian Brain Initiative

Author

Carter, Adrian, primary, Richards, Linda J., additional, Apthorp, Deborah, additional, Azghadi, Mostafa Rahimi, additional, Badcock, David R., additional, Balleine, Bernard, additional, Bekkers, John M., additional, Berk, Michael, additional, Bourne, James A., additional, Bradley, Andrew P., additional, Breakspear, Michael, additional, Brichta, Alan, additional, Carter, Olivia, additional, Castles, Anne, additional, Chakli, Khaled, additional, Cohen-Woods, Sarah, additional, Conn, Simon J., additional, Cornish, Jennifer, additional, Cornish, Kim, additional, de Zubicaray, Greg, additional, Egan, Gary F., additional, Enticott, Peter G., additional, Fitzgibbon, Bernadette M., additional, Forlini, Cynthia, additional, Fornito, Alex, additional, Griffiths, Lyn, additional, Gullifer, Judith, additional, Hall, Wayne, additional, Halliday, Glenda, additional, Hannan, Anthony J., additional, Harrer, Stefan, additional, Harvey, Alan, additional, Hatherly, Chris, additional, Hickie, Ian B., additional, Kennett, Jeanette, additional, Kiernan, Matthew, additional, Kilpatrick, Trevor, additional, Kiral-Kornek, Isabell, additional, Korgaonkar, Mayuresh S., additional, Lawrence, Andrew J., additional, Leventer, Rick, additional, Levy, Neil, additional, Licinio, Julio, additional, Lovell, Nigel, additional, Mackellar, Geoff, additional, Malcolm, Lynne, additional, Mason, Alice, additional, Mattingley, Jason B., additional, Medland, Sarah E., additional, Michie, Patricia T., additional, Nithianantharajah, Jess, additional, Parker, John, additional, Payne, Jonathan M., additional, Poole-Warren, Laura, additional, Sah, Pankaj, additional, Sarnyai, Zoltan, additional, Schofield, Peter R., additional, Shimoni, Olga, additional, Shum, David H.K., additional, Silk, Tim, additional, Slee, Mark, additional, Smith, Ashleigh E., additional, Soulis, Tina, additional, Sriram, Sharath, additional, Stuart, Greg J., additional, Tapson, Jonathan, additional, Thompson, Matthew B., additional, van Schaik, André, additional, Vincent, Nicole A., additional, Vissel, Bryce, additional, and Waters, Allison, additional

Published
2020
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39. A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation

Author

Conn, Vanessa M., Hugouvieux, Veronique, Nayak, Aditya, Conos, Stephanie A., Capovilla, Giovanna, Cildir, Gokhan, Jourdain, Agnes, Tergaonkar, Vinay, Schmid, Markus, Zubieta, Chloe, Conn, Simon J., Conn, Vanessa M., Hugouvieux, Veronique, Nayak, Aditya, Conos, Stephanie A., Capovilla, Giovanna, Cildir, Gokhan, Jourdain, Agnes, Tergaonkar, Vinay, Schmid, Markus, Zubieta, Chloe, and Conn, Simon J.

Abstract

Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life(1), yet their functions have remained elusive. Here, we report that circRNAs can be used as bona fide biomarkers of functional, exon-skipped AS variants in Arabidopsis, including in the homeotic MADS-box transcription factor family. Furthermore, we demonstrate that circRNAs derived from exon 6 of the SEPALLATA3 (SEP3) gene increase abundance of the cognate exon-skipped AS variant (SEP3.3 which lacks exon 6), in turn driving floral homeotic phenotypes. Toward demonstrating the underlying mechanism, we show that the SEP3 exon 6 circRNA can bind strongly to its cognate DNA locus, forming an RNA: DNA hybrid, or R-loop, whereas the linear RNA equivalent bound significantly more weakly to DNA. R-loop formation results in transcriptional pausing, which has been shown to coincide with splicing factor recruitment and AS(2-4). This report presents a novel mechanistic insight for how at least a subset of circRNAs probably contribute to increased splicing efficiency of their cognate exon-skipped messenger RNA and provides the first evidence of an organismal-level phenotype mediated by circRNA manipulation.

Published
2017
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41. The Non-Coding RNA Journal Club: Highlights on Recent Papers—7.

Author

Hua Xiao, Shiu, Patrick K. T., Gabryleska, Marta, Conn, Simon J., Dey, Abhishek, Chakrabarti, Kausik, Regouc, Manuel, Pichler, Martin, Vang Ørom, Ulf Andersson, Santulli, Gaetano, Satoshi Nishiwada, Goel, Ajay, Nagarajan, Vaishnavi, Timmons, Lisa, Alahari, Suresh K., Laprovitera, Noemi, Ferracin, Manuela, Po Hu, and Hailing Jin

Subjects
NON-coding RNA, RNA splicing, LIFE sciences, MOLECULAR biology, BOTANY, LINCRNA
Published
2019
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42. The Non-Coding RNA Journal Club: Highlights on Recent Papers--6.

Author

Hua Xiao, Shiu, Patrick K. T., Jun Shu, Santulli, Gaetano, Gheybi, Mohammad K., Conn, Simon J., Bogard, Baptiste, Hubé, Florent, Taube, Joseph H., Mani, Sendurai A., Luo Song, Calin, George A., and Shuxing Zhang

Subjects
NON-coding RNA, MICRORNA, EXOSOMES, HOSTS (Biology), CELL membranes
Published
2018
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44. An update on magnesium homeostasis mechanisms in plants

Author

Hermans, Christian, Conn, Simon J, Chen, Jiugeng, Xiao, Qiying, Verbruggen, Nathalie, Hermans, Christian, Conn, Simon J, Chen, Jiugeng, Xiao, Qiying, and Verbruggen, Nathalie

Abstract

Worldwide, nearly two-thirds of the population do not consume the recommended amount of magnesium (Mg) in their diet. Furthermore, low Mg status (hypomagnesaemia) is known to contribute to a number of human chronic disease conditions. Because the principal dietary Mg source is of plant origin, agronomic and genetic biofortification strategies are aimed at improving nutritional Mg content in food crops to overcome this mineral deficiency in humans. This update incorporates the contributions of annotated permeases involved in Mg uptake, storage and recycling with a schematic model of Mg movement at the organ and cellular levels in the model species Arabidopsis thaliana. Furthermore, approaches using mutagenesis or natural ionomic variation to identify loci involved in Mg homeostasis in roots, leaves and seeds will be summarised. A brief overview will be presented on how Arabidopsis research can help to develop strategies for biofortification of crops., info:eu-repo/semantics/published

Published
2013

45. Intra- and interchromosomal contact mapping reveals the Ighlocus has extensive conformational heterogeneity and interacts with B-lineage genes

Author

Mielczarek, Olga, Rogers, Carolyn H., Zhan, Yinxiu, Matheson, Louise S., Stubbington, Michael J.T., Schoenfelder, Stefan, Bolland, Daniel J., Javierre, Biola M., Wingett, Steven W., Várnai, Csilla, Segonds-Pichon, Anne, Conn, Simon J., Krueger, Felix, Andrews, Simon, Fraser, Peter, Giorgetti, Luca, and Corcoran, Anne E.

Abstract

To produce a diverse antibody repertoire, immunoglobulin heavy-chain (Igh) loci undergo large-scale alterations in structure to facilitate juxtaposition and recombination of spatially separated variable (VH), diversity (DH), and joining (JH) genes. These chromosomal alterations are poorly understood. Uncovering their patterns shows how chromosome dynamics underpins antibody diversity. Using tiled Capture Hi-C, we produce a comprehensive map of chromatin interactions throughout the 2.8-Mb Ighlocus in progenitor B cells. We find that the Ighlocus folds into semi-rigid subdomains and undergoes flexible looping of the VHgenes to its 3′ end, reconciling two views of locus organization. Deconvolution of single Ighlocus conformations using polymer simulations identifies thousands of different structures. This heterogeneity may underpin the diversity of V(D)J recombination events. All three immunoglobulin loci also participate in a highly specific, developmentally regulated network of interchromosomal interactions with genes encoding B cell-lineage factors. This suggests a model of interchromosomal coordination of B cell development.

Published
2023
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46. The RNAinteractome in the Hallmarks of Cancer

Author

Gabryelska, Marta M. and Conn, Simon J.

Abstract

Ribonucleic acid (RNA) molecules are indispensable for cellular homeostasis in healthy and malignant cells. However, the functions of RNA extend well beyond that of a protein‐coding template. Rather, both coding and non‐coding RNA molecules function through critical interactions with a plethora of cellular molecules, including other RNAs, DNA, and proteins. Deconvoluting this RNA interactome, including the interacting partners, the nature of the interaction, and dynamic changes of these interactions in malignancies has yielded fundamental advances in knowledge and are emerging as a novel therapeutic strategy in cancer. Here, we present an RNA‐centric review of recent advances in the field of RNA–RNA, RNA–protein, and RNA–DNA interactomic network analysis and their impact across the Hallmarks of Cancer. This article is categorized under:RNA in Disease and Development > RNA in DiseaseRNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes Interactions of RNA molecules play key roles across all Hallmarks of Cancer and were not captured by large genome sequencing efforts. These RNA interactomics provide novel insight into cancer initiation and progression, and provide novel therapeutic targets for treatment of cancers and many other diseases.

Published
2023
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47. Protocol: optimising hydroponic growth systems for nutritional and physiological analysis of Arabidopsis thaliana and other plants

Author

Conn, Simon J, primary, Hocking, Bradleigh, additional, Dayod, Maclin, additional, Xu, Bo, additional, Athman, Asmini, additional, Henderson, Sam, additional, Aukett, Lucy, additional, Conn, Vanessa, additional, Shearer, Monique K, additional, Fuentes, Sigfredo, additional, Tyerman, Stephen D, additional, and Gilliham, Matthew, additional

Published
2013
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