The Transcriptional Regulatory Mechanisms Exploration of Jujube Biological Traits through Multi-omics Analysis DOI Open Access
Shulin Zhang, Zhuo Chen,

Luying Feng

et al.

Published: Jan. 29, 2024

Jujube (Ziziphus jujuba Mill.) stands as a pivotal fruit tree with significant economic, ecological, and social value. Recent years have witnessed remarkable strides in multi-omics-based biological re-search on jujube. This review began by summarizing advancements jujube genomics. Subse-quently, we provided comprehensive overview of the integrated application genomics, tran-scriptomics, metabolomics to explore genes governing domestication traits, quality attributes (including sugar synthesis, terpenoids, flavonoids), responses abiotic stress, discussed transcriptional regulatory mechanisms underlying these traits. Further-more, challenges multi-omics research traits were outlined, pro-posed integration resources such pan-genomics sRNAome unearth key molecules networks influencing diverse Incorporating into practical breeding strategies, including gene editing, transgenic approaches, progressive breeding, holds potential for achieving molecular-design efficient genetic en-hancement

Language: Английский

Past, present, and future of CRISPR genome editing technologies DOI Creative Commons

Martin Pacesa,

Oana Pelea, Martin Jínek

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(5), P. 1076 - 1100

Published: Feb. 1, 2024

Genome editing has been a transformative force in the life sciences and human medicine, offering unprecedented opportunities to dissect complex biological processes treat underlying causes of many genetic diseases. CRISPR-based technologies, with their remarkable efficiency easy programmability, stand at forefront this revolution. In Review, we discuss current state CRISPR gene technologies both research therapy, highlighting limitations that constrain them technological innovations have developed recent years address them. Additionally, examine summarize landscape applications context health therapeutics. Finally, outline potential future developments could shape coming years.

Language: Английский

Citations

126
Sequence modeling and design from molecular to genome scale with Evo DOI

Eric Nguyen,

Michael Poli, Matthew G. Durrant

et al.

Science, Journal Year: 2024, Volume and Issue: 386(6723)

Published: Nov. 14, 2024

The genome is a sequence that encodes the DNA, RNA, and proteins orchestrate an organism’s function. We present Evo, long-context genomic foundation model with frontier architecture trained on millions of prokaryotic phage genomes, report scaling laws DNA to complement observations in language vision. Evo generalizes across proteins, enabling zero-shot function prediction competitive domain-specific models generation functional CRISPR-Cas transposon systems, representing first examples protein-RNA protein-DNA codesign model. also learns how small mutations affect whole-organism fitness generates megabase-scale sequences plausible architecture. These capabilities span molecular scales complexity, advancing our understanding control biology.

Language: Английский

Citations

58
Sequence modeling and design from molecular to genome scale with Evo DOI Creative Commons
Éric Nguyen, Michael Poli, Matthew G. Durrant

et al.

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

Published: Feb. 27, 2024

The genome is a sequence that completely encodes the DNA, RNA, and proteins orchestrate function of whole organism. Advances in machine learning combined with massive datasets genomes could enable biological foundation model accelerates mechanistic understanding generative design complex molecular interactions. We report Evo, genomic enables prediction generation tasks from to scale. Using an architecture based on advances deep signal processing, we scale Evo 7 billion parameters context length 131 kilobases (kb) at single-nucleotide, byte resolution. Trained prokaryotic genomes, can generalize across three fundamental modalities central dogma biology perform zero-shot competitive with, or outperforms, leading domain-specific language models. also excels multi-element tasks, which demonstrate by generating synthetic CRISPR-Cas complexes entire transposable systems for first time. information learned over predict gene essentiality nucleotide resolution generate coding-rich sequences up 650 kb length, orders magnitude longer than previous methods. multi-modal multi-scale provides promising path toward improving our control multiple levels complexity.

Language: Английский

Citations

52
Discovery of Diverse CRISPR-Cas Systems and Expansion of the Genome Engineering Toolbox DOI Creative Commons
Eugene V. Koonin, Jonathan S. Gootenberg, Omar O. Abudayyeh

et al.

Biochemistry, Journal Year: 2023, Volume and Issue: 62(24), P. 3465 - 3487

Published: May 16, 2023

CRISPR systems mediate adaptive immunity in bacteria and archaea through diverse effector mechanisms have been repurposed for versatile applications therapeutics diagnostics thanks to their facile reprogramming with RNA guides. RNA-guided CRISPR-Cas targeting interference are mediated by effectors that either components of multisubunit complexes class 1 or multidomain single-effector proteins 2. The compact 2 broadly adopted multiple applications, especially genome editing, leading a transformation the molecular biology biotechnology toolkit. diversity enzymes, initially limited Cas9 nuclease, was substantially expanded via computational metagenome mining include numerous variants Cas12 Cas13, providing substrates development versatile, orthogonal tools. Characterization these uncovered many new features, including distinct protospacer adjacent motifs (PAMs) expand space, improved editing specificity, rather than DNA targeting, smaller crRNAs, staggered blunt end cuts, miniature promiscuous cleavage, etc. These unique properties enabled such as harnessing RNase activity type VI effector, supersensitive nucleic acid detection. well, despite challenge expressing delivering multiprotein effectors. rich enzymes led rapid maturation toolbox, capabilities gene knockout, base prime insertion, imaging, epigenetic modulation, transcriptional editing. Combined rational design engineering associated RNAs, natural related bacterial provides vast resource expanding repertoire tools biotechnology.

Language: Английский

Citations

51
Evolutionary origins of archaeal and eukaryotic RNA-guided RNA modification in bacterial IS110 transposons DOI
Hugo Vaysset, Chance Meers, Jean Cury

et al.

Nature Microbiology, Journal Year: 2025, Volume and Issue: 10(1), P. 20 - 27

Published: Jan. 2, 2025

Language: Английский

Citations

2
DNA targeting by compact Cas9d and its resurrected ancestor DOI Creative Commons
Rodrigo Fregoso Ocampo, Jack P. K. Bravo, Tyler L. Dangerfield

et al.

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

Published: Jan. 7, 2025

Abstract Type II CRISPR endonucleases are widely used programmable genome editing tools. Recently, CRISPR-Cas systems with highly compact nucleases have been discovered, including Cas9d (a type II-D nuclease). Here, we report the cryo-EM structures of a nuclease (747 amino acids in length) multiple functional states, revealing stepwise process DNA targeting involving conformational switch REC2 domain insertion. Our provide insights into intricately folded guide RNA which acts as structural scaffold to anchor small, flexible protein domains for recognition. The sgRNA can be truncated by up ~25% yet still retain activity vivo. Using ancestral sequence reconstruction, generated capable efficient mammalian cells. Collectively, our results mechanistic evolution and diverse systems, providing blueprint future re-engineering minimal RNA-guided endonucleases.

Language: Английский

Citations

2
Programmable RNA-guided DNA endonucleases are widespread in eukaryotes and their viruses DOI Creative Commons
Kaiyi Jiang, Justin Lim,

Samantha R. Sgrizzi

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(39)

Published: Sept. 27, 2023

Programmable RNA-guided DNA nucleases perform numerous roles in prokaryotes, but the extent of their spread outside prokaryotes is unclear. Fanzors, eukaryotic homolog prokaryotic TnpB proteins, have been detected genomes eukaryotes and large viruses, activity functions remain unknown. Here, we characterize Fanzors as RNA-programmable endonucleases, using biochemical cellular evidence. We found diverse that frequently associate with various transposases. Reconstruction evolution revealed multiple radiations RuvC-containing homologs eukaryotes. Fanzor genes captured introns proteins acquired nuclear localization signals, indicating extensive, long-term adaptation to functioning cells. contain a rearranged catalytic site RuvC domain, similar distinct subset TnpBs, lack collateral cleavage activity. demonstrate can be harnessed for genome editing human cells, highlighting potential these widespread biotechnology applications.

Language: Английский

Citations

30
De novo gene synthesis by an antiviral reverse transcriptase DOI
Stephen Tang, Valentin Conte, Dennis J. Zhang

et al.

Science, Journal Year: 2024, Volume and Issue: 386(6717)

Published: Aug. 8, 2024

Defense-associated reverse transcriptase (DRT) systems perform DNA synthesis to protect bacteria against viral infection, but the identities and functions of their products remain largely unknown. We show that DRT2 encode an unprecedented immune pathway involves de novo gene through rolling circle transcription a noncoding RNA (ncRNA). Programmed template jumping on ncRNA generates concatemeric cDNA, which becomes double-stranded upon infection. This product constitutes protein-coding, nearly endless open reading frame ( neo ) whose expression leads potent cell growth arrest, restricting Our work highlights elegant expansion genome coding potential RNA-templated creation challenges conventional paradigms genetic information encoded along one-dimensional axis genomic DNA.

Language: Английский

Citations

14
Mobile genetic elements mediate the cross-media transmission of antibiotic resistance genes from pig farms and their risks DOI

Zhendi Yu,

Zishu Liu,

Lingtao Sun

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 926, P. 172115 - 172115

Published: April 1, 2024

Language: Английский

Citations

9
Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes DOI Creative Commons
Peter H. Yoon, Petr Skopintsev, Honglue Shi

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(22), P. 12414 - 12427

Published: Nov. 16, 2023

RNA-guided endonucleases form the crux of diverse biological processes and technologies, including adaptive immunity, transposition, genome editing. Some these enzymes are components insertion sequences (IS) in IS200/IS605 IS607 transposon families. Both IS families encode a TnpA transposase TnpB nuclease, an enzyme ancestral to CRISPR-Cas12s. In eukaryotes, homologs occur as two distinct types, Fanzor1s Fanzor2s. We analyzed evolutionary relationships between prokaryotic TnpBs eukaryotic Fanzors, which revealed that both Fanzor2s stem from single lineage with unusual active site arrangement. The widespread nature Fanzors implies properties this particular were particularly suited adaptation eukaryotes. Biochemical analysis common strategies employed by co-evolve their cognate transposases. Collectively, our results provide new model sequential evolution Fanzor2s, details how genes origin evolve give rise protein

Language: Английский

Citations

20