The RNA exosome maintains cellular RNA homeostasis by controlling transcript abundance in the brain DOI Creative Commons
Lauryn Higginson, Xingjun Wang, Kevin He

et al.

Published: Oct. 30, 2024

Abstract Intracellular ribonucleases (RNases) are essential in all aspects of RNA metabolism, including maintaining accurate levels. Inherited mutations genes encoding ubiquitous RNases associated with human diseases, primarily affecting the nervous system. Recessive an evolutionarily conserved RNase complex, exosome, lead to syndromic neurodevelopmental disorders characterized by progressive neurodegeneration, such as Pontocerebellar Hypoplasia Type 1b (PCH1b). We establish a CRISPR/Cas9-engineered Drosophila model PCH1b study cell-type-specific post-transcriptional regulatory functions nuclear exosome complex within fly head tissue. Here, we report that pathogenic alter activity causing widespread dysregulation brain-enriched cellular transcriptomes, rRNA processing defects—resulting tissue-specific, neurodegenerative effects flies. These findings provide comprehensive understanding function developed animal brain and underscore critical role machinery homeostasis brain.

Language: Английский

Genome-wide quantification of RNA flow across subcellular compartments reveals determinants of the mammalian transcript life cycle DOI
Robert Ietswaart,

Brendan M. Smalec,

Albert Xu

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(14), P. 2765 - 2784.e16

Published: July 1, 2024

Language: Английский

Citations

26
The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation DOI Creative Commons
Li Zhang, Jian‐Shu Wang,

Zhidong Tang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 17, 2025

Nuclear RNA decay has emerged as a mechanism for post-transcriptional gene regulation in cultured cells. However, whether this process occurs animals and holds biological relevance remains largely unexplored. Here, we demonstrate that MTR4, the central cofactor of nuclear exosome, is essential embryogenesis spermatogenesis. Embryonic development Mtr4 knockout mice arrests at 6.5 day. Germ cell-specific results male infertility with specific severe defect meiotic initiation. During pre-meiotic stage, MTR4/exosome represses genes, which are typically shorter size possess fewer introns, through degradation. Concurrently, it ensures expression mitotic genes generally exhibiting opposite features. Consistent these rules, mature replication-dependent histone mRNAs polyadenylated retrotransposon RNAs were identified targets germ In addition, MTR4 regulates alternative splicing many genes. Together, our work underscores importance degradation regulating germline transcriptome, ensuring appropriate program transition from mitosis to meiosis during cells, but its role unclear. authors found exosome co-factor functions shaping transcriptome initiation fertility.

Language: Английский

Citations

0
LncRNA XLOC-040580 targeted by TPRA1 coordinate zygotic genome activation during porcine embryonic development DOI Creative Commons
Mengxin Liu,

Enhong Li,

Haiyuan Mu

et al.

Cell Transplantation, Journal Year: 2025, Volume and Issue: 34

Published: April 1, 2025

Long noncoding RNAs (lncRNAs) are crucial in porcine preimplantation embryonic development, yet their regulatory role during zygote genome activation (ZGA) is poorly understood. We analyzed transcriptome data from fetal fibroblasts (PEF), induced pluripotent stem cells (iPS), and embryos, identifying ZGA-specific lncRNAs like XLOC-040580, further predicted its potentially interacting genes TPRA1 BCL2L1 via co-expression network. XLOC-040580 was knocked down by siRNA microinjection the expression of ZGA-related detected qRT-PCR. After microinjecting targeting at one-cell stage, we counted blastocyst development rate. The rate consistent with results si-XLOC-040580 after si-TPRA1. Through dual-luciferase reporter assays, found that a downstream target TPRA1. To elucidate mechanism Single-cell mRNA sequencing knockdown revealed network involved developmental defects. Transcriptome analysis specifically expressed activation. Knockdown decreased reduced both total cell number TE number. were co-expressed ZGA could interact promoter region regulate expression. or blocked affecting genes. validated lncRNA played key process, which regulated These implied functional axis TPRA1-XLOC-040580-downstream functions also coordinated early porcine.

Language: Английский

Citations

0
Biomolecular liquid‒liquid phase separation associated with repetitive genomic elements DOI
Sefan Asamitsu, Yuka W. Iwasaki

Polymer Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Language: Английский

Citations

0
Ginseng in Delaying Brain Aging: Progress and perspectives DOI
Jingwen Niu, Guoqi Zhu, Junjie Zhang

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156587 - 156587

Published: March 1, 2025

Language: Английский

Citations

0
RNA surveillance by the RNA helicase MTR4 determines volume of mouse oocytes DOI

Yun‐Wen Wu,

Zuo‐Qi Deng,

Rong Yan

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

1
Unveiling the mystery of nuclear RNA homeostasis DOI

Shan Lin,

Ling‐Ling Chen

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(5), P. 583 - 585

Published: May 1, 2024

Language: Английский

Citations

0
Co-transcriptional RNA processing boosts zygotic gene activation DOI

Jingzhao Xu,

Xiaojing Li, Xiaowen Hao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 15, 2024

Summary Transcription decodes protein-coding genes and interprets regulatory information embedded in the genome by generating RNA. In eukaryotes, gene transcription is coupled with RNA processing via carboxyl terminal domain (CTD) of polymerase (Pol) II, which enhances messenger (mRNA) production. We propose that co-transcriptional essential for zygotic activation (ZGA), transitioning program from noncoding to after fertilization. Truncating CTD mouse cells disrupts this coupling, halting global mRNA synthesis increasing (ncRNA) levels through enhanced intergenic stabilization. truncation also triggers epigenetic reprogramming nuclear reorganization towards totipotency, resembling early cleavage embryos. Mechanistically, restrains nonproductive activity sequences, while at requiring processing, it promotes elongation facilitating promoter-proximal pausing, directionality, velocity. Longer lengths enhance activity, likely evolving accommodate sequences mammalian genomes.

Language: Английский

Citations

0
Cells transit through a quiescent-like state to convert to neurons at high rates DOI Creative Commons
Adam M. Beitz,

JMY Teves,

Conrad Oakes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Abstract While transcription factors (TFs) provide essential cues for directing and redirecting cell fate, TFs alone are insufficient to drive cells adopt alternative fates. Rather, rely on receptive states induce novel identities. Cell state emerges from is shaped by cellular history the activity of diverse processes. Here, we define molecular properties a highly amenable factor-mediated direct conversion fibroblasts induced motor neurons. Using well-defined model post-mitotic identify proliferative, that transiently during conversion. Through examining chromatin accessibility, histone marks, nuclear features, find reprogram characterized global reductions in size transcriptional activity. Supported globally increased levels H3K27me3, enter quiescent-like reduced RNA metabolism elevated expression REST p27, markers quiescent neural stem cells. From this transient state, convert neurons at high rates. Inhibition Ezh2, catalytic subunit PRC2 deposits abolishes Our work offers roadmap changes processes with different potentials may generalize other cell-fate transitions. Highlights Proliferation drives compact TF-mediated Increased receptivity corresponds volumes. Reprogrammable display global, genome-wide increases H3K27me3. High H3K27me3 support cells’ transits through altered metabolism. Ezh2 size, reduces quiescence marker p27. Acute inhibition neuron One Sentence Summary Cells transit Graphical

Language: Английский

Citations

0
The RNA exosome maintains cellular RNA homeostasis by controlling transcript abundance in the brain DOI Creative Commons
Lauryn Higginson, Xingjun Wang, Kevin He

et al.

Published: Oct. 30, 2024

Abstract Intracellular ribonucleases (RNases) are essential in all aspects of RNA metabolism, including maintaining accurate levels. Inherited mutations genes encoding ubiquitous RNases associated with human diseases, primarily affecting the nervous system. Recessive an evolutionarily conserved RNase complex, exosome, lead to syndromic neurodevelopmental disorders characterized by progressive neurodegeneration, such as Pontocerebellar Hypoplasia Type 1b (PCH1b). We establish a CRISPR/Cas9-engineered Drosophila model PCH1b study cell-type-specific post-transcriptional regulatory functions nuclear exosome complex within fly head tissue. Here, we report that pathogenic alter activity causing widespread dysregulation brain-enriched cellular transcriptomes, rRNA processing defects—resulting tissue-specific, neurodegenerative effects flies. These findings provide comprehensive understanding function developed animal brain and underscore critical role machinery homeostasis brain.

Language: Английский

Citations

0