Walking a tightrope: The complex balancing act of R-loops in genome stability

Molecular Cell, Год журнала: 2022, Номер 82(12), С. 2267 - 2297

Опубликована: Май 3, 2022

Язык: Английский

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RNA polymerase II speed: a key player in controlling and adapting transcriptome composition

The EMBO Journal, Год журнала: 2021, Номер 40(15)

Опубликована: Июль 13, 2021

RNA polymerase II (RNA Pol II) speed or elongation rate, i.e., the number of nucleotides synthesized per unit time, is a major determinant transcriptome composition. It controls co-transcriptional processes such as splicing, polyadenylation, and transcription termination, thus regulating production alternative splice variants, circular RNAs, alternatively polyadenylated transcripts, read-through transcripts. itself regulated in response to intra- extra-cellular stimuli can turn affect composition these stimuli. Evidence points potentially important role modification through regulation for adaptation cells changing environment, pointing function cellular physiology. Analyzing dynamics may therefore be central fully understand physiological processes, development multicellular organisms. Recent findings also raise possibility that deregulation detrimental participate disease progression. Here, we review initial current approaches measure speed, well providing an overview factors controlling which are affected. Finally, discuss cell

Язык: Английский

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Structural basis of nucleosome disassembly and reassembly by RNAPII elongation complex with FACT

Science, Год журнала: 2022, Номер 377(6611)

Опубликована: Авг. 18, 2022

During gene transcription, RNA polymerase II (RNAPII) traverses nucleosomes in chromatin, but the mechanism has remained elusive. Using cryo–electron microscopy, we obtained structures of RNAPII elongation complex (EC) passing through a nucleosome presence transcription factors Spt6, Spn1, Elf1, Spt4/5, and Paf1C histone chaperone FACT (facilitates chromatin transcription). The show snapshots EC progression on DNA mediating downstream disassembly, followed by its reassembly upstream EC, which is facilitated FACT. dynamically adapts to successively occurring subnucleosome intermediates, forming an interface with EC. form “cradle” at DNA-exit site support reassembly. These explain while maintaining structure epigenetic information.

Язык: Английский

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U1 snRNP increases RNA Pol II elongation rate to enable synthesis of long genes

Molecular Cell, Год журнала: 2023, Номер 83(8), С. 1264 - 1279.e10

Опубликована: Март 24, 2023

Язык: Английский

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R-loops at microRNA encoding loci promote co-transcriptional processing of pri-miRNAs in plants

Nature Plants, Год журнала: 2022, Номер 8(4), С. 402 - 418

Опубликована: Апрель 21, 2022

In most organisms, the maturation of nascent RNAs is coupled to transcription. Unlike in animals, RNA polymerase II (RNAPII) transcribes microRNA genes (MIRNAs) as long and structurally variable pri-miRNAs plants. Current evidence suggests that miRNA biogenesis complex assembly initiates early during transcription However, it unknown whether processing occurs co-transcriptionally. Here, we used native elongating transcript sequencing data imaging techniques demonstrate plant We found entire co-transcriptionally for processed from loop hairpin but requires a second nucleoplasmic step those base. Furthermore, co- post-transcriptional mechanisms co-exist miRNAs dynamic balance. Notably, discovered R-loops, formed near start site region MIRNAs, promote co-transcriptional pri-miRNA processing. our results suggest neofunctionalization miRNAs, boosting countless regulatory scenarios.

Язык: Английский

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Supercoiling-mediated feedback rapidly couples and tunes transcription

Cell Reports, Год журнала: 2022, Номер 41(3), С. 111492 - 111492

Опубликована: Окт. 1, 2022

Transcription induces a wave of DNA supercoiling, altering the binding affinity RNA polymerases and reshaping biochemical landscape gene regulation. As supercoiling rapidly diffuses, transcription dynamically reshapes regulation proximal genes, forming complex feedback loop. However, theoretical framework is needed to integrate biophysical with transcriptional To investigate role supercoiling-mediated within multi-gene systems, we model under influence polymerase dynamics, allowing us identify patterns expression that result from physical inter-gene coupling. We find syntax—the relative ordering orientation genes—defines profiles, variance, burst correlation two-gene systems. Furthermore, can enhance or weaken Our results suggest couples behavior between neighboring providing regulatory mechanism tunes variance in engineered networks explains co-localized native circuits.

Язык: Английский

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Secondary structures in RNA synthesis, splicing and translation

Computational and Structural Biotechnology Journal, Год журнала: 2022, Номер 20, С. 2871 - 2884

Опубликована: Янв. 1, 2022

Even though the functional role of mRNA molecules is primarily decided by nucleotide sequence, several properties are determined secondary structure conformations. Examples structures include long range interactions, hairpins, R-loops and G-quadruplexes they formed through interactions non-adjacent nucleotides. Here, we discuss advances in our understanding how can impact RNA synthesis, splicing, translation half-life. During determine polymerase II (RNAPII) speed, thereby influencing splicing. Splicing also binding proteins their rates modulated structures. For initiation translation, control choice start site. highlight mechanisms which modulate these processes, technologies to detect study them systematically, consider roles disease.

Язык: Английский

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Chloroplast gene expression: Recent advances and perspectives

Plant Communications, Год журнала: 2023, Номер 4(5), С. 100611 - 100611

Опубликована: Май 4, 2023

Chloroplasts evolved from an ancient cyanobacterial endosymbiont more than 1.5 billion years ago. During subsequent coevolution with the nuclear genome, chloroplast genome has remained independent, albeit strongly reduced, its own transcriptional machinery and distinct features, such as chloroplast-specific innovations to gene expression complicated post-transcriptional processing. Light activates of genes via mechanisms that optimize photosynthesis, minimize photodamage, prioritize energy investments. Over past few years, studies have moved stage describing phases explore underlying mechanisms. In this review, we focus on recent advances emerging principles govern in land plants. We discuss PPR protein engineering biotechnological impacts RNA research, new techniques for elucidating molecular expression, some important aspects improving crop yield stress tolerance. also remaining biological mechanistic questions be answered future.

Язык: Английский

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Transcription–Replication Conflicts as a Source of Genome Instability

Annual Review of Genetics, Год журнала: 2023, Номер 57(1), С. 157 - 179

Опубликована: Авг. 8, 2023

Transcription and replication both require large macromolecular complexes to act on a DNA template, yet these machineries cannot simultaneously the same sequence. Conflicts between transcription (transcription–replication conflicts, or TRCs) are widespread in prokaryotes eukaryotes have capacity cause damage compromise complete, faithful of genome. This review will highlight recent studies investigating genomic locations TRCs mechanisms by which they may be prevented, mitigated, resolved. We address work from model organisms mammalian systems but predominantly focus multicellular owing additional complexities inherent coordination context cell type–specific gene expression higher-order chromatin organization.

Язык: Английский

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Pre-mRNA splicing and its cotranscriptional connections

Trends in Genetics, Год журнала: 2023, Номер 39(9), С. 672 - 685

Опубликована: Май 24, 2023

Язык: Английский

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