The physiology of alternative splicing

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(4), P. 242 - 254

Published: Oct. 13, 2022

Language: Английский

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Phase Separation as a Missing Mechanism for Interpretation of Disease Mutations

Cell, Journal Year: 2020, Volume and Issue: 183(7), P. 1742 - 1756

Published: Dec. 1, 2020

Language: Английский

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The science of puromycin: From studies of ribosome function to applications in biotechnology

Computational and Structural Biotechnology Journal, Journal Year: 2020, Volume and Issue: 18, P. 1074 - 1083

Published: Jan. 1, 2020

Puromycin is a naturally occurring aminonucleoside antibiotic that inhibits protein synthesis by ribosome-catalyzed incorporation into the C-terminus of elongating nascent chains, blocking further extension and resulting in premature termination translation. It most commonly known as selection marker for cell lines genetically engineered to express resistance transgene, but its additional uses probe have proven invaluable across wide variety model systems, ranging from purified ribosomes cell-free translation intact cultured cells whole animals. comprised nucleoside covalently bound an amino acid, mimicking 3′ end aminoacylated tRNAs participate delivery acids ribosomes. Both moieties can tolerate some chemical substitutions modifications without significant loss activity, generating diverse toolbox puromycin-based reagents with added functionality, such biotin affinity purification or fluorophores fluorescent microscopy detection. These reagents, well anti-puromycin antibodies, played pivotal role advancing our understanding regulation dysregulation normal pathological processes, including immune response neurological function. This manuscript reviews current state research, structure mechanism action, relevant derivatives, use advanced methodologies major insights generated using techniques both lab clinic.

Language: Английский

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Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(4), P. 251 - 269

Published: Dec. 16, 2022

Language: Английский

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Nanopore sequencing of brain-derived full-length circRNAs reveals circRNA-specific exon usage, intron retention and microexons

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Aug. 10, 2021

Abstract Circular RNA (circRNA) is a class of covalently joined non-coding RNAs with functional roles in wide variety cellular processes. Their composition shows extensive overlap exons found linear mRNAs making it difficult to delineate their using short-read sequencing, particularly for long and multi-exonic circRNAs. Here, we use long-read nanopore sequencing nicked circRNAs (circNick-LRS) characterize total 18,266 39,623 human mouse brain, respectively. We further develop an approach targeted panel (circPanel-LRS), eliminating the need prior circRNA enrichment find >30 isoforms on average per locus. Our data show that exhibit large number splicing events such as novel exons, intron retention microexons preferentially occur propose altered exon usage may reflect resistance nonsense-mediated decay absence translation.

Language: Английский

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RNA-binding proteins in neurological development and disease

RNA Biology, Journal Year: 2020, Volume and Issue: 18(7), P. 972 - 987

Published: Aug. 30, 2020

RNA-binding proteins are a critical group of multifunctional that precisely regulate all aspects gene expression, from alternative splicing to mRNA trafficking, stability, and translation. Converging evidence highlights aberrant RNA metabolism as common pathogenic mechanism in several neurodevelopmental neurodegenerative diseases. However, dysregulation disease-linked results widespread, often tissue-specific and/or pleiotropic effects on the transcriptome, making it challenging determine underlying cellular molecular mechanisms contribute disease pathogenesis. Understanding how misregulation well alterations stability localization impact activity function neuronal is fundamental addressing defects synaptic dysfunction disease. Here we highlight recent exciting studies use high-throughput transcriptomic analysis advanced genetic, cell biological, imaging approaches dissect role different processing steps. We focus specifically efforts elucidate functional consequences morphology, plasticity development also consider new areas investigation will achieve spatiotemporal control expression for homeostasis plasticity.

Language: Английский

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Puromycin reactivity does not accurately localize translation at the subcellular level

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Aug. 26, 2020

Puromycin is a tyrosyl-tRNA mimic that blocks translation by labeling and releasing elongating polypeptide chains from translating ribosomes. has been used in molecular biology research for decades as inhibitor. The development of puromycin antibodies derivatized analogs enabled the quantification active bulk single-cell assays. More recently, vivo puromycylation assays have become popular tools localizing ribosomes cells. These often use elongation inhibitors to purportedly inhibit release puromycin-labeled nascent peptides Using vitro experiments various eukaryotic systems, we demonstrate that, even presence inhibitors, puromycylated are released diffuse away Puromycylation reveal subcellular sites, such nuclei, where accumulate post-release which do not necessarily coincide with sites translation. Our findings urge caution when interpreting vivo.

Language: Английский

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RNA-binding proteins balance brain function in health and disease

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(3), P. 1309 - 1370

Published: Oct. 1, 2020

Posttranscriptional gene expression including splicing, RNA transport, translation, and decay provides an important regulatory layer in many if not all molecular pathways. Research the last decades has positioned RNA-binding proteins (RBPs) right center of posttranscriptional regulation. Here, we propose interdependent networks RBPs to regulate complex pathways within central nervous system (CNS). These are involved multiple aspects neuronal development functioning, higher cognition. Therefore, it is sufficient unravel individual contribution a single RBP its consequences but rather study understand tight interplay between different RBPs. In this review, summarize recent findings field biology discuss Second, emphasize underlying dynamics network how might key processes such as neurogenesis, synaptic transmission, plasticity. Importantly, envision that dysfunction specific could lead perturbation network. This would have direct indirect (compensatory) effects mRNA binding translational control leading global changes cellular programs general plasticity particular. focus on cause neuropsychiatric neurodegenerative disorders. Based findings, alterations entire account for phenotypic dysfunctions observed diseases neurodegeneration, epilepsy, autism spectrum

Language: Английский

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Chromatin-mediated alternative splicing regulates cocaine-reward behavior

Neuron, Journal Year: 2021, Volume and Issue: 109(18), P. 2943 - 2966.e8

Published: Sept. 1, 2021

Language: Английский

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The nexus between RNA-binding proteins and their effectors

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(5), P. 276 - 294

Published: Nov. 23, 2022

Language: Английский

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