Results 71 to 80 of about 12,575 (173)

Targeting the Spliceosomal Protein USP39 Through Allosteric Ligands and PROTAC‐Induced Degradation

Angewandte Chemie International Edition, Volume 65, Issue 5, 28 January 2026.
Proteolysis‐targeting chimeras (PROTACs) enable degradation of proteins previously considered undruggable by harnessing the cellular ubiquitin–proteasome system. In this study, Schäfer et al. identify thiazole‐based small molecules that allosterically bind the zinc finger domain of ubiquitin‐specific protease 39 (USP39), a non‐enzymatic scaffold ...
Daniel Schäfer, Cristian Prieto‐Garcia, Jianhui Wang, Marcel Heinz, Vigor Matkovic, Pavel Kielkowski, Sebastian Hasselbeck, Varun Jayeshkumar Shah, Stefan Knapp, Gerhard Hummer, Ivan Dikic, Xinlai Cheng   +11 more
wiley   +1 more source

In vivo kinetics of U4/U6·U5 tri-snRNP formation in Cajal bodies

Molecular Biology of the Cell, 2011
The U4/U6·U5 tri-small nuclear ribonucleoprotein particle (tri-snRNP) is an essential pre-mRNA splicing factor, which is assembled in a stepwise manner before each round of splicing. It was previously shown that the tri-snRNP is formed in Cajal bodies (CBs), but little is known about the dynamics of this process. Here we created a mathematical model of
Novotný, I. (Ivan), Blažíková, M. (Michaela), Staněk, D. (David), Heřman, P., Malínský, J. (Jan)   +4 more
openaire   +3 more sources

Neurochondrin promotes U5 snRNP maturation by regulating AAR2 release from PRPF8

Nucleic Acids Research
Pre-mRNA splicing is orchestrated by the spliceosome, a dynamic and highly regulated ribonucleoprotein complex composed of five small nuclear ribonucleoproteins (snRNPs). Despite extensive studies, the biogenesis of snRNPs remains incompletely understood.
Tingrong Ren, Wanru Huang, Gaigai Wei, Haiping Zhao, Yuqi Zhang, Jingjing Yi, Zhihan Guo, Yihan Wang, Jiating Kuang, Zhaoying Sheng, Huiling Zhang, Duanwu Zhang   +11 more
semanticscholar   +1 more source

Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets

MedComm, Volume 6, Issue 12, December 2025.
Alternative splicing (AS) expands proteomic diversity and functional complexity in eukaryotes, regulated by spliceosomal components, RNA elements, and epigenetic modifications. Dysregulated AS contributes to diseases, including cancer, neurodegenerative disorders, and cardiovascular conditions, among others. Therapeutic interventions, such as antisense
Zhi‐Min Zhu, Xiao‐Mei Wu, Yan Hu, Xiao‐Lan Bian, Ya‐Qin Wang, Qiong‐Ni Zhu   +5 more
wiley   +1 more source

Characterization of WAC interactions with R2TP and TTT chaperone complexes linking glucose and glutamine availability to mTORC1 activity

FEBS Open Bio, Volume 15, Issue 11, Page 1771-1788, November 2025.
TTT and R2TP chaperone complexes are required for the assembly and activation of mTORC1. WAC directly interacts with components of TTT, R2TP, and mTORC1, and these interactions are affected by the availability of glucose and glutamine, correlating with changes in mTORC1 activity.
Sofía Cabezudo, Natalia Cuervo, Carmen García‐Martín, Andrés López‐Perrote, Clara Reglero, Adrián Maqueda‐Real, Ana González‐Corpas, Marina Serna, Diego Megías, Alejo Efeyan, Solip Park, Oscar Llorca   +11 more
wiley   +1 more source

Transcription-dependent colocalization of the U1, U2, U4/U6, and U5 snRNPs in coiled bodies [PDF]

The Journal of cell biology, 1992
We have recently shown that discrete foci are present in the nuclei of mammalian cells in which each of the U1, U2, U4/U6, and U5 snRNPs involved in pre-mRNA splicing, and the non-snRNP-splicing factor U2AF, are concentrated (Carmo-Fonseca, M., D. Tollervey, R. Pepperkok, S. Barabino, A. Merdes, C. Brunner, P. D. Zamore, M. R. Green, E. Hurt, and A. I.
Carmo-Fonseca, M., Pepperkok, R., Carvalho, M. T., Lamond, A. I.   +3 more
openaire   +3 more sources

Mining Alzheimer's Interactomes, Macromolecular Complexes and Pathways for Drug Discovery

PROTEOMICS, Volume 25, Issue 21-22, Page 102-150, November 2025.
ABSTRACT Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia. Many cases are diagnosed annually and there is no currently available cure. Understanding the underlying disease biology of AD through the study of molecular networks, particularly by mapping clinical variants to tissue‐specific interactomes and ...
Kalpana Panneerselvam, Krishna Kumar Tiwari, Luana Licata, Simona Panni, Sylvie Ricard‐Blum, Sucharitha Balu, Susie Huget, Juan Jose Medina Reyes, Eliot Ragueneau, Livia Perfetto, Birgit Meldal, Sandra Orchard, Henning Hermjakob   +12 more
wiley   +1 more source

Genetic screening for Arabidopsis mutants defective in STA1 regulation under thermal stress implicates the existence of regulators of its specific expression, and the genetic interactions in the stress signaling pathways

Frontiers in Plant Science, 2016
To cope with environmental stresses, plants have developed various stress tolerance mechanisms that involve the induction of many stress responsive genes through stress-specific and common signaling pathways. Stress-specific/common transcription factors,
Si-in eYu, Jin-Hee eHan, Chanvotey eChhoeun, Byeong-ha eLee   +3 more
doaj   +1 more source

Liquid–Liquid Phase Separation: Mechanisms, Roles, and Implications in Cellular Function and Disease

FASEB BioAdvances, Volume 7, Issue 11, November 2025.
Liquid–liquid phase separation (LLPS) is a fundamental biophysical process responsible for forming membraneless organelles involved in key cellular functions like chromatin organization and gene expression. Dysregulation of LLPS contributes to various diseases, including neurodegenerative disorders.
Dikesh Kumar Thakur, Sonal Padole, Tapati Sarkar, Somasundaram Arumugam, Shiladitya Chattopadhyay   +4 more
wiley   +1 more source

The network of protein–protein interactions within the human U4/U6.U5 tri-snRNP [PDF]

RNA, 2006
The human 25S U4/U6.U5 tri-snRNP is a major building block of the U2-type spliceosome and contains, in addition to the U4, U6, and U5 snRNAs, at least 30 distinct proteins. To learn more about the molecular architecture of the tri-snRNP, we have investigated interactions between tri-snRNP proteins using the yeast two-hybrid assay and in vitro binding ...
Liu, S., Rauhut, R., Vornlocher, H., Luehrmann, R.   +3 more
openaire   +3 more sources