PubMed HealthSearch

Biomedical subjects

Yujie Zhang

Publications and source records attributed to Yujie Zhang.

3 recordsLinked to original sources

DREAMS illuminates spatial DNA and RNA modification landscapes.

DNA and RNA modifications regulate gene expression and RNA processing, but their spatial organization in complex tissues remains elusive. Here we developed DNA RNA Elements Areal Mass Spectrometry (DREAMS), a mass spectrometry imaging platform that spatially maps diverse nucleic acid modifications simultaneously. Applying DREAMS to TET-deficient mouse brains (Tet1Δ/Δ and triple Tet1/2/3Δ/Δ), we uncover TET1's unexpected role in modulating N1-methyladenosine (m1A), a pivotal RNA modification. While DREAMS reveals broad modification landscapes altered across TET knockouts, we identify TET1-mediated changes in m1A that correlate with transcriptome alterations. Our work establishes DREAMS as a transformative tool for spatial epigenomics/epitranscriptomics and suggests that TET enzymes could influence multiple DNA and RNA modifications with potential gatekeeping roles in nucleic acid regulation.

Animals

Mobile genetic elements-driven partitions of mega-plasmids resistome in Salmonella Infantis.

Salmonella enterica serovar Infantis (S. Infantis) becomes the primary pathogen among the top Salmonella serotypes, contributing to numerous cases of foodborne illness annually in the United States. S. Infantis infection has spread rapidly worldwide, especially the clones with pESI-like plasmids. However, the underlying mechanisms regarding the transmission of S. Infantis, particularly mobile genetic elements (MGEs), mediated horizontal gene transfer, are limited. The objective of this study was to evaluate the relationship, if any, among MGEs, antibiotic-resistant genes (ARGs), and virulence factors (VFs) within S. Infantis via genomic analysis. A total of 91 S. Infantis complete genomes with high sequencing quality were selected for downstream bioinformatic analysis. The results showed that the majority of VFs were located in the bacterial chromosomes, while most ARGs were carried by S. Infantis mega-plasmids in an MGE-favored manner. Integrons and transposons were closely associated with certain ARGs, but prophages within mega-plasmids displayed a diverse ARG profile. Collectively, MGE-mediated horizontal gene transfer might lead to ARG acquisition by mega-plasmids, subsequently contributing to the resistome of S. Infantis. Our findings provide insights into the development of MGE-associated resistome in S. Infantis that could inform more effective prevention and intervention strategies to control this pathogen, further ensuring public health and safety.IMPORTANCEThe rapid emergence and transmission of antibiotic-resistant foodborne pathogens pose a significant risk to public health, necessitating the discovery of underlying mechanisms to control multidrug-resistant pathogens. Salmonella enterica serovar Infantis (S. Infantis) has become a pathogen of clinical and epidemiological relevance in recent years, ranking as the top prevalent serovar associated with foodborne illnesses and exhibiting resistance to several antibiotics. The current investigation of multidrug resistance (MDR) S. Infantis strains primarily emphasized the presence of mega-plasmids. However, the question of how mega-plasmids contribute to the transmission of antibiotic-resistant genes (ARG) is unaddressed. Utilizing the genomic characterization of S. Infantis complete genomes with high quality, our study revealed that the resistome of S. Infantis mega-plasmids-the primary ARG reservoirs of S. Infantis-followed a specific pattern of mobile genetic elements (MGEs). Monitoring the spread of MGE-carried ARGs within mega-plasmids should be considered in future surveillance.

Interspersed Repetitive Sequences

Proper 5'-3' cotranslational mRNA decay in yeast requires import of Xrn1 to the nucleus.

The budding yeast Xrn1 protein shuttles between the nucleus, where it stimulates transcription, and the cytoplasm, where it executes the major cytoplasmic mRNA decay. In the cytoplasm, apart from catalyzing 5'→3' decay onto non translated mRNAs, Xrn1 can follow the last translating ribosome to degrade the decapped mRNA template, a process known as "cotranslational mRNA decay". We have previously observed that the import of Xrn1 to the nucleus is required for efficient cytoplasmic mRNA decay. Here by using an Xrn1 mutant that cannot enter the nucleus, but is otherwise functional in ribonuclease activity, we show that nuclear import is necessary for proper global cotranslational decay of mRNAs along coding regions and also affects degradation in the of 5' region of a large group of mRNAs, which comprise about 20% of the transcriptome. Furthermore, a principal component analysis of the genomic datasets of this mutant and other Xrn1 mutants also shows that lack of a cytoplasmic 5'→3' exoribonuclease is the primary cause of the physiological defects seen in a xrn1Δ mutant, but also suggests that Xrn1 import into the nucleus is necessary for its full in vivo functions.

Exoribonucleases