DEAD-box ATPase Dbp2 is the key enzyme in an mRNP assembly checkpoint at the 3’-end of genes and involved in the recycling of cleavage factors DOI Creative Commons
Ebru Aydin,

Silke Schreiner,

Jacqueline Böhme

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 9, 2024

Abstract mRNA biogenesis in the eukaryotic nucleus is a highly complex process. The numerous RNA processing steps are tightly coordinated to ensure that only fully processed transcripts released from chromatin for export nucleus. Here, we present hypothesis fission yeast Dbp2, ribonucleoprotein (RNP) remodelling ATPase of DEAD-box family, key enzyme an RNP assembly checkpoint at 3’-end genes. We show Dbp2 interacts with cleavage and polyadenylation (CPAC) localises bodies, which enriched factors proteins involved nuclear surveillance. Upon loss 3’-processed, polyadenylated RNAs accumulate on CPAC components depleted soluble pool. Under these conditions, cells display increased likelihood skip sites delayed transcription termination, suggesting levels free insufficient maintain normal processing. Our data support model active component mRNP licenses coupled release.

Язык: Английский

Bento: a toolkit for subcellular analysis of spatial transcriptomics data DOI Creative Commons
Clarence K. Mah, Noorsher Ahmed, Nicole A. Lopez

и другие.

Genome biology, Год журнала: 2024, Номер 25(1)

Опубликована: Апрель 2, 2024

Abstract The spatial organization of molecules in a cell is essential for their functions. While current methods focus on discerning tissue architecture, cell–cell interactions, and expression patterns, they are limited to the multicellular scale. We present Bento, Python toolkit that takes advantage single-molecule information enable analysis at subcellular Bento ingests molecular coordinates segmentation boundaries perform three analyses: defining domains, annotating localization quantifying gene–gene colocalization. demonstrate MERFISH, seqFISH + , Molecular Cartography, Xenium datasets. part open-source Scverse ecosystem, enabling integration with other single-cell tools.

Язык: Английский

Процитировано

25
A kinetic dichotomy between mitochondrial and nuclear gene expression processes DOI
Erik McShane, Mary Couvillion, Robert Ietswaart

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(8), С. 1541 - 1555.e11

Опубликована: Март 18, 2024

Язык: Английский

Процитировано

23
Pre-mRNA splicing order is predetermined and maintains splicing fidelity across multi-intronic transcripts DOI
Karine Choquet, Autum R. Baxter‐Koenigs,

Sarah-Luisa Dülk

и другие.

Nature Structural & Molecular Biology, Год журнала: 2023, Номер 30(8), С. 1064 - 1076

Опубликована: Июль 13, 2023

Язык: Английский

Процитировано

21
Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression DOI
Nicholas J. Kramer, Gyan Prakash, R. Stefan Isaac

и другие.

Nature Cell Biology, Год журнала: 2023, Номер 25(11), С. 1575 - 1589

Опубликована: Сен. 28, 2023

Язык: Английский

Процитировано

20
grandR: a comprehensive package for nucleotide conversion RNA-seq data analysis DOI Creative Commons
Teresa Rummel, Lygeri Sakellaridi, Florian Erhard

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 15, 2023

Metabolic labeling of RNA is a powerful technique for studying the temporal dynamics gene expression. Nucleotide conversion approaches greatly facilitate generation data but introduce challenges their analysis. Here we present grandR, comprehensive package quality control, differential expression analysis, kinetic modeling, and visualization such data. We compare several existing methods inference synthesis rates half-lives using progressive time courses. demonstrate need recalibration effective times Bayesian approach to study snapshot experiments.

Язык: Английский

Процитировано

15
Halfpipe: a tool for analyzing metabolic labeling RNA-seq data to quantify RNA half-lives DOI Creative Commons

Jason M. Müller,

Elisabeth Altendorfer,

Susanne Freier

и другие.

NAR Genomics and Bioinformatics, Год журнала: 2025, Номер 7(1)

Опубликована: Янв. 7, 2025

Abstract We introduce Halfpipe, a tool for analyzing RNA-seq data from metabolic RNA labeling experiments. Its main features are the absolute quantification of 4-thiouridine-labeling-induced T>C conversions in as generated by SLAM-seq, calculating proportion newly synthesized transcripts, and estimating subcellular half-lives. Halfpipe excels at correcting critical biases caused typically low efficiency. measure compare metabolism G1 phase during mitosis synchronized human cells. find that half-lives constantly expressed RNAs similar phase, suggesting stability those genes is constant throughout cell cycle. Our estimates correlate well with literature values known sequence features. freely available https://github.com/IMSBCompBio/Halfpipe.

Язык: Английский

Процитировано

0
Profiling transcriptome composition and dynamics within nuclear compartments using SLAM-RT&Tag DOI Creative Commons
Nadiya Khyzha, Kami Ahmad, Steven Henikoff

и другие.

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Nuclear compartments are membrane-less regions enriched in functionally related molecules. RNA is a major component of many nuclear compartments, but the identity and dynamics transcripts within poorly understood. Here, we applied reverse transcribe tagment (RT&Tag) to human cell lines identify transcript populations Polycomb domains speckles. We also developed SLAM-RT&Tag, which combines metabolic labeling with RT&Tag, quantify compartments. observed unique differing structures each compartment. Intriguingly, exceptionally long genes transcribed adjacent transiently associated chromatin. By contrast, speckles act as quality control checkpoints that confine incompletely spliced polyadenylated facilitate their post-transcriptional splicing. In summary, demonstrate at undergo distinct processing mechanisms, highlighting pivotal role compartmentalization maturation.

Язык: Английский

Процитировано

0
Uncovering the isoform-resolution kinetic landscape of nonsense-mediated mRNA decay with EZbakR DOI Creative Commons
Justin W. Mabin, Isaac W. Vock, Martin Machyna

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Cellular RNA levels are a product of synthesis and degradation kinetics, which can differ among transcripts the same gene. An important cause isoform-specific decay is nonsense-mediated mRNA (NMD) pathway, degrades with premature termination codons (PTCs) other features. Understanding NMD functions requires strategies to quantify isoform kinetics; however, current approaches remain limited. Methods like nucleotide-recoding RNA-seq (NR-seq) enable insights into but existing bioinformatic tools do not provide robust, rate constant estimates. We extend EZbakR-suite by implementing strategy infer isoform-level kinetics from short-read NR-seq data. This approach uncovers unexpected variability in efficiency conserved PTC-containing exons rapid subset mRNAs lacking PTCs. Our findings highlight effects competition between pathways, mechanistic established correlates, identify transcript features promoting efficient decay.

Язык: Английский

Процитировано

0
Gene-specific transcript buffering revealed by perturbation of coactivator complexes DOI Creative Commons

Faezeh Forouzanfar,

David F. Moreno, Damien Plassard

и другие.

Science Advances, Год журнала: 2025, Номер 11(12)

Опубликована: Март 19, 2025

Transcript buffering entails reciprocal modulation of mRNA synthesis and degradation to maintain stable RNA levels under varying cellular conditions. Current models depict a global connection between degradation, but underlying mechanisms remain unclear. Here, we show that changes in metabolism following depletion TIP60/KAT5, the acetyltransferase subunit NuA4 transcriptional coactivator complex, reveal transcript occurs at gene-specific level. By combining sequencing nuclear, cytoplasmic, newly synthesized fractions with biophysical modeling mouse embryonic stem cells, demonstrate caused by TIP60 are offset corresponding nuclear export cytoplasmic stability, indicating buffering. Disruption unrelated ATAC complex also causes We propose cells dynamically adjust splicing, export, response individual alterations, thereby sustaining homeostasis.

Язык: Английский

Процитировано

0
Coupling mechanisms coordinating mRNA translation with stages of the mRNA lifecycle DOI Creative Commons
Valeria Famà, Lucia Coscujuela Tarrero,

Roberto Albanese

и другие.

RNA Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Gene expression involves a series of consequential processes, beginning with mRNA synthesis and culminating in translation. Traditionally studied as linear sequence events, recent findings challenge this perspective, revealing coupling mechanisms that coordinate key steps gene expression, even when spatially temporally distant. In review, we focus on translation, the final stage examine its stages metabolism: synthesis, processing, export, decay. For each these provide an overview known instances Furthermore, discuss role high-throughput technologies uncovering intricate interactions genome-wide scale. Finally, highlight challenges propose future directions to advance our understanding how orchestrate robust adaptable programs.

Язык: Английский

Процитировано

0