RNA‐mediated heterochromatin formation at repetitive elements in mammals DOI Creative Commons
Nikolaos Stamidis, Jan J. Żylicz

The EMBO Journal, Год журнала: 2023, Номер 42(8)

Опубликована: Фев. 27, 2023

The failure to repress transcription of repetitive genomic elements can lead catastrophic genome instability and is associated with various human diseases. As such, multiple parallel mechanisms cooperate ensure repression heterochromatinization these elements, especially during germline development early embryogenesis. A vital question in the field how specificity establishing heterochromatin at achieved. Apart from trans-acting protein factors, recent evidence points a role different RNA species targeting repressive histone marks DNA methylation sites mammals. Here, we review discoveries on this topic predominantly focus methylation, piRNAs, other localized satellite RNAs.

Язык: Английский

Alternative splicing in EMT and TGF-β signaling during cancer progression DOI
Ying E. Zhang, Christina H. Stuelten

Seminars in Cancer Biology, Год журнала: 2024, Номер 101, С. 1 - 11

Опубликована: Апрель 15, 2024

Язык: Английский

Процитировано

16
A CPF-like phosphatase module links transcription termination to chromatin silencing DOI Creative Commons
Eduardo Mateo‐Bonmatí, Miguel Montez, Robert Maple

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(12), С. 2272 - 2286.e7

Опубликована: Июнь 1, 2024

Язык: Английский

Процитировано

12
Synthetic circRNA therapeutics: innovations, strategies, and future horizons DOI Creative Commons

Jingsheng Cai,

Zonghao Qiu,

William C. Cho

и другие.

MedComm, Год журнала: 2024, Номер 5(11)

Опубликована: Ноя. 1, 2024

Abstract Small molecule drugs are increasingly emerging as innovative and effective treatments for various diseases, with mRNA therapeutics being a notable representative. The success of COVID‐19 vaccines has underscored the transformative potential in RNA therapeutics. Within family, there is another unique type known circRNA. This single‐stranded closed‐loop offers advantages over mRNA, including enhanced stability prolonged protein expression, which may significantly impact therapeutic strategies. Furthermore, circRNA plays pivotal role pathogenesis such cancers, autoimmune disorders, cardiovascular making it promising clinical intervention target. Despite these benefits, application settings remains underexplored. review provides comprehensive overview current state synthetic therapeutics, focusing on its synthesis, optimization, delivery, diverse applications. It also addresses challenges impeding advancement from bench to bedside. By summarizing aspects, aims equip researchers insights into ongoing developments future directions Highlighting both progress existing gaps research, this valuable perspectives advancing field guiding investigations.

Язык: Английский

Процитировано

10
DDX41 coordinates RNA splicing and transcriptional elongation to prevent DNA replication stress in hematopoietic cells DOI Creative Commons
Satoru Shinriki,

Mayumi Hirayama,

Akiko Nagamachi

и другие.

Leukemia, Год журнала: 2022, Номер 36(11), С. 2605 - 2620

Опубликована: Окт. 14, 2022

Abstract Myeloid malignancies with DDX41 mutations are often associated bone marrow failure and cytopenia before overt disease manifestation. However, the mechanisms underlying these specific conditions remain elusive. Here, we demonstrate that loss of function impairs efficient RNA splicing, resulting in DNA replication stress excess R-loop formation. Mechanistically, binds to 5′ splice site (5′SS) coding coordinates splicing transcriptional elongation; prevents splicing-coupled transient pausing polymerase II at 5ʹSS, causing aberrant formation transcription-replication collisions. Although degree acquired S phase is small, cells undergo mitosis under-replicated being remained, micronuclei significant damage, thus leading impaired cell proliferation genomic instability. These processes may be responsible for phenotypes mutations.

Язык: Английский

Процитировано

30
Multifunctional histone variants in genome function DOI
Lee H. Wong, David J. Tremethick

Nature Reviews Genetics, Год журнала: 2024, Номер unknown

Опубликована: Авг. 13, 2024

Язык: Английский

Процитировано

9
A Revision of Herpes Simplex Virus Type 1 Transcription: First, Repress; Then, Express DOI Creative Commons
Laura Dunn, Claire Birkenheuer, Joel D. Baines

и другие.

Microorganisms, Год журнала: 2024, Номер 12(2), С. 262 - 262

Опубликована: Янв. 26, 2024

The herpes virus genome bears more than 80 strong transcriptional promoters. Upon entry into the host cell nucleus, these genes are transcribed in an orderly manner, producing five immediate–early (IE) gene products, including ICP0, ICP4, and ICP22, while non-IE mostly silent. IE products necessary for transcription of temporal classes following sequentially as early, leaky late, true late. A recent analysis using precision nuclear run-on followed by deep sequencing (PRO-seq) has revealed important step preceding all HSV-1 transcription. Specifically, proteins ICP4 ICP0 enter with incoming to help preclude nascent antisense, intergenic, sense viral genes. VP16, which is also delivered nucleus upon entry, almost immediately reverses this repression on resulting de novo expression ICP22 further repress early late through different mechanisms before sequential de-repression later infection. This repression, termed transient protein-mediated (TIEMR), precludes unproductive, infection ensure efficient progression cascade.

Язык: Английский

Процитировано

7
Epigenetic regulation of human non-coding RNA gene transcription DOI
Marco Morselli, Giorgio Dieci

Biochemical Society Transactions, Год журнала: 2022, Номер 50(2), С. 723 - 736

Опубликована: Март 14, 2022

Recent investigations on the non-protein-coding transcriptome of human cells have revealed previously hidden layers gene regulation relying regulatory (nc) RNAs, including widespread ncRNA-dependent epigenetic chromatin states and mRNA translation stability. However, despite its centrality, ncRNA genes has received relatively little attention. In this mini-review, we attempt to provide a synthetic account recent literature suggesting an unexpected complexity in chromatin-dependent transcription by three nuclear RNA polymerases. Emerging common features, like heterogeneity within multigene families their influence 3D genome organization, point unexplored issues whose investigation could lead better understanding whole epigenomic network.

Язык: Английский

Процитировано

26
Transcript elongation by RNA polymerase II in plants: factors, regulation and impact on gene expression DOI Creative Commons
Simon Obermeyer,

Henna Kapoor,

Hanna Markusch

и другие.

The Plant Journal, Год журнала: 2023, Номер 118(3), С. 645 - 656

Опубликована: Янв. 27, 2023

Transcriptional elongation by RNA polymerase II (RNAPII) through chromatin is a dynamic and highly regulated step of eukaryotic gene expression. A combination transcript factors (TEFs) including modulators RNAPII activity histone chaperones facilitate efficient transcription on nucleosomal templates. Biochemical genetic analyses, primarily performed in Arabidopsis, provided insight into the contribution TEFs to establish expression patterns during plant growth development. In addition summarising role expression, we emphasise our review recent advances field. Thus, mechanisms are presented how aberrant intragenic initiation suppressed repressing transcriptional start sites within coding sequences. We also discuss interference ongoing with neighbouring genes prevented. Moreover, it appears that plants make no use promoter-proximal pausing way mammals do, but there nucleosome-defined mechanism(s) determine efficiency mRNA synthesis RNAPII. Accordingly, still growing number processes related growth, development responses changing environmental conditions prove be at level elongation.

Язык: Английский

Процитировано

16
PTBP1-activated co-transcriptional splicing controls epigenetic status of pluripotent stem cells DOI Creative Commons

Camilla Iannone,

Yaroslav Kainov, Anna Zhuravskaya

и другие.

Molecular Cell, Год журнала: 2023, Номер 83(2), С. 203 - 218.e9

Опубликована: Янв. 1, 2023

Many spliceosomal introns are excised from nascent transcripts emerging RNA polymerase II (RNA Pol II). The extent of cell-type-specific regulation and possible functions such co-transcriptional events remain poorly understood. We examined the role RNA-binding protein PTBP1 in this process using an acute depletion approach followed by analysis chromatin- II-associated transcripts. show that activates excision hundreds introns, a surprising effect given is known to promote intron retention. Importantly, some co-transcriptionally activated fail complete their splicing without PTBP1. In striking example, retention PTBP1-dependent triggers nonsense-mediated decay encoding DNA methyltransferase DNMT3B. provide evidence facilitates natural decline DNMT3B levels developing neurons protects differentiation-specific genes ectopic methylation. Thus, PTBP1-activated widespread phenomenon mediating epigenetic control cellular identity.

Язык: Английский

Процитировано

14
The fidelity of transcription in human cells DOI Creative Commons
Claire Chung, Bert M. Verheijen, Xinmin Zhang

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(5)

Опубликована: Янв. 25, 2023

To determine the error rate of transcription in human cells, we analyzed transcriptome H1 embryonic stem cells with a circle-sequencing approach that allows for high-fidelity sequencing transcriptome. These experiments identified approximately 100,000 errors distributed over every major RNA species cells. Our results indicate different display rates, suggesting prioritize fidelity some RNAs others. Cross-referencing detected various genetic and epigenetic features genome revealed vivo changes along length transcript is further modified by context, repetitive elements, markers, speed transcription. suggest BRCA1, DNA repair protein implicated breast cancer, has previously unknown role suppression errors. Finally, distribution multiple tissues new mouse model found they occur preferentially neurons, compared to other cell types. observations lend additional weight idea play key progression neurological disorders, including Alzheimer's disease.

Язык: Английский

Процитировано

14