Sperm epigenetic alterations contribute to inter- and transgenerational effects of paternal exposure to long-term psychological stress via evading offspring embryonic reprogramming DOI Creative Commons
Xiaoguo Zheng, Zhenhua Li,

Guishuan Wang

et al.

Cell Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: Oct. 27, 2021

Paternal life experiences impact offspring health via germline, and epigenetic inheritance provides a potential mechanism. However, global reprogramming during embryogenesis gametogenesis represents the largest hurdle to conceptualize it. Yet, detailed characterization of how sperm alterations carrying "environmental memory" can evade embryonic remains elusive. Here, mice exposed long-term restraint stress were employed study mechanisms underlying inter- transgenerational effects paternal exposure psychological stress. We found that could induce reproductive, behavioral, metabolic disorders. Bisulfite methylation profiling 18 12 embryo samples three consecutive generations identified Differential DNA Methylation Regions (DMRs) at frequencies ~11.36% 0.48%, respectively. These DMRs related genes with functional implications for response, tissue these passed disorders epigenetically offspring. More importantly, evaded through erasure subsequent reestablishment, but not un-erasure way. Nonetheless, their reestablishment proportions in primitive streak (E7.5) stage altered. Furthermore, sncRNA-seq revealed stress-induced tsRNA, miRNA rsRNA dysregulation might play important roles occurrence inheritance. finding implied contribute stress, highlighted possible molecular

Language: Английский

Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics DOI
Takayuki Nojima, Nicholas Proudfoot

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(6), P. 389 - 406

Published: Jan. 25, 2022

Language: Английский

Citations

299
Origins and evolving functionalities of tRNA-derived small RNAs DOI
Qi Chen, Xudong Zhang, Junchao Shi

et al.

Trends in Biochemical Sciences, Journal Year: 2021, Volume and Issue: 46(10), P. 790 - 804

Published: May 27, 2021

Language: Английский

Citations

152
Exploring the expanding universe of small RNAs DOI
Junchao Shi, Tong Zhou, Qi Chen

et al.

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(4), P. 415 - 423

Published: April 1, 2022

Language: Английский

Citations

134
TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer DOI Creative Commons
Zhangli Su, Ida Monshaugen, Briana Wilson

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 20, 2022

Abstract RNA modifications are important regulatory elements of functions. However, most genome-wide mapping has focused on messenger RNAs and transfer RNAs, but such datasets have been lacking for small RNAs. Here we mapped N 1 -methyladenosine (m A) in the cellular space. Benchmarked with synthetic m A our workflow identified specific groups A-containing which otherwise disproportionally under-represented. In particular, 22-nucleotides long 3′ tRNA-fragments highly enriched TRMT6/61A-dependent located within seed region. negatively affects gene silencing by tRF-3s. urothelial carcinoma bladder, where TRMT6/61A is over-expressed, higher modification tRFs detected, correlated a dysregulation tRF targetome. Lastly, regulates tRF-3 targets involved unfolded protein response. Together, results reveal mechanism regulating expression via base RNA.

Language: Английский

Citations

88
Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development DOI Creative Commons
Ariane Lismer, Sarah Kimmins

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 14, 2023

Abstract Although more studies are demonstrating that a father’s environment can influence child health and disease, the molecular mechanisms underlying non-genetic inheritance remain unclear. It was previously thought sperm exclusively contributed its genome to egg. More recently, association have shown various environmental exposures including poor diet, toxicants, stress, perturbed epigenetic marks in at important reproductive developmental loci were associated with offspring phenotypes. The cellular routes underlie how transmitted fertilization, resist reprogramming embryo, drive phenotypic changes only now beginning be unraveled. Here, we provide an overview of state field intergenerational paternal mammals present new insights into relationship between embryo development three pillars inheritance: chromatin, DNA methylation, non-coding RNAs. We evaluate compelling evidence sperm-mediated transmission retention embryo. Using landmark examples, discuss sperm-inherited regions may escape impact via implicate transcription factors, chromatin organization, transposable elements. Finally, link paternally functional pre- post-implantation Understanding factors will permit greater understanding related origins disease.

Language: Английский

Citations

82
Emerging roles of tRNA-derived fragments in cancer DOI Creative Commons
Min Fu, Jianmei Gu,

Maoye Wang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 13, 2023

Abstract tRNA-derived fragments (tRFs) are an emerging category of small non-coding RNAs that generated from cleavage mature tRNAs or tRNA precursors. The advance in high-throughput sequencing has contributed to the identification increasing number tRFs with critical functions distinct physiological and pathophysiological processes. can regulate cell viability, differentiation, homeostasis through multiple mechanisms thus considered as regulators human diseases including cancer. In addition, evidence suggest extracellular may be utilized promising diagnostic prognostic biomarkers for cancer liquid biopsy. this review, we focus on biogenesis, classification modification tRFs, summarize multifaceted emphasis current research status perspectives

Language: Английский

Citations

66
A standardized ontology for naming tRNA-derived RNAs based on molecular origin DOI
Andrew Holmes, Patricia P. Chan, Qi Chen

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(5), P. 627 - 628

Published: March 3, 2023

Language: Английский

Citations

63
Small RNA modifications: regulatory molecules and potential applications DOI Creative Commons
Qunli Xiong, Yaguang Zhang

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 22, 2023

Abstract Small RNAs (also referred to as small noncoding RNAs, sncRNA) are defined polymeric ribonucleic acid molecules that less than 200 nucleotides in length and serve a variety of essential functions within cells. RNA species include microRNA (miRNA), PIWI-interacting (piRNA), interfering (siRNA), tRNA-derived (tsRNA), etc. Current evidence suggest can also have diverse modifications their nucleotide composition affect stability well capacity for nuclear export, these relevant drive molecular signaling processes biogenesis, cell proliferation differentiation. In this review, we highlight the characteristics cellular modifications, current techniques reliable detection. We discuss how may be clinical applications diagnosis treatment human health conditions such cancer.

Language: Английский

Citations

55
Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice DOI Creative Commons
Jingwei Liu, Junchao Shi, Rebecca Hernandez

et al.

Environment International, Journal Year: 2023, Volume and Issue: 172, P. 107769 - 107769

Published: Jan. 23, 2023

Exposure to ubiquitous plastic-associated endocrine disrupting chemicals (EDCs) is associated with the increased risk of many chronic diseases. For example, phthalate exposure cardiometabolic mortality in humans, societal costs ∼ $39 billion/year or more. We recently demonstrated that several widely used EDCs increase disease appropriate mouse models. In addition affecting adult health, parental has also been shown cause metabolic disorders, including obesity and diabetes, offspring. While most studies have focused on impact maternal EDC offspring's little known about effects paternal exposure. current study, we investigated adverse a but understudied phthalate, dicyclohexyl (DCHP) health F1 F2 offspring mice. Paternal DCHP led exacerbated insulin resistance impaired signaling without diet-induced obesity. previously showed sperm small non-coding RNAs tRNA-derived (tsRNAs) rRNA-derived (rsRNAs) contribute intergenerational transmission paternally acquired disorders. Using novel PANDORA-seq, revealed can lead tsRNA/rsRNA landscape changes were undetected by traditional RNA-seq, which may DCHP-elicited effects. Lastly, found sex-specific transgenerational elicited glucose intolerance female descendants. Our results suggest phthalates their These findings our understanding etiology human diseases originating from chemical-elicited

Language: Английский

Citations

47
tRNA renovatio: Rebirth through fragmentation DOI Creative Commons
Bernhard Kuhle, Qi Chen, Paul Schimmel

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(22), P. 3953 - 3971

Published: Oct. 5, 2023

tRNA function is based on unique structures that enable mRNA decoding using anticodon trinucleotides. These interact with specific aminoacyl-tRNA synthetases and ribosomes 3D shape sequence signatures. Beyond translation, tRNAs serve as versatile signaling molecules interacting other RNAs proteins. Through evolutionary processes, fragmentation emerges not merely random degradation but an act of recreation, generating shorter called tRNA-derived small (tsRNAs). tsRNAs exploit their linear sequences newly arranged for unexpected biological functions, epitomizing the "renovatio" (from Latin, meaning renewal, renovation, rebirth). Emerging methods to uncover full tRNA/tsRNA modifications, combined techniques study RNA integrate AI-powered predictions, will comprehensive investigations products new interaction potentials in relation functions. We anticipate these directions herald a era understanding complexity advancing pharmaceutical engineering.

Language: Английский

Citations

47