We study computational and experimental RNA biology.

@article{pmid36449563,

title = {Single-Cell Analysis in Lung Adenocarcinoma Implicates RNA Editing in Cancer Innate Immunity and Patient Prognosis},

author = {Tracey W Chan and Jack P Dodson and Jaron Arbet and Paul C Boutros and Xinshu Xiao},

doi = {10.1158/0008-5472.CAN-22-1062},

issn = {1538-7445},

year  = {2023},

date = {2023-02-01},

journal = {Cancer Res},

volume = {83},

number = {3},

pages = {374--385},

abstract = {RNA editing modifies single nucleotides of RNAs, regulating primary protein structure and protein abundance. In recent years, the diversity of proteins and complexity of gene regulation associated with RNA editing dysregulation has been increasingly appreciated in oncology. Large-scale shifts in editing have been observed in bulk tumors across various cancer types. However, RNA editing in single cells and individual cell types within tumors has not been explored. By profiling editing in single cells from lung adenocarcinoma biopsies, we found that the increased editing trend of bulk lung tumors was unique to cancer cells. Elevated editing levels were observed in cancer cells resistant to targeted therapy, and editing sites associated with drug response were enriched. Consistent with the regulation of antiviral pathways by RNA editing, higher editing levels in cancer cells were associated with reduced antitumor innate immune response, especially levels of natural killer cell infiltration. In addition, the level of RNA editing in cancer cells was positively associated with somatic point mutation burden. This observation motivated the definition of a new metric, RNA editing load, reflecting the amount of RNA mutations created by RNA editing. Importantly, in lung cancer, RNA editing load was a stronger predictor of patient survival than DNA mutations. This study provides the first single cell dissection of editing in cancer and highlights the significance of RNA editing load in cancer prognosis.



SIGNIFICANCE: RNA editing analysis in single lung adenocarcinoma cells uncovers RNA mutations that correlate with tumor mutation burden and cancer innate immunity and reveals the amount of RNA mutations that strongly predicts patient survival. See related commentary by Luo and Liang, p. 351.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37027465,

title = {Widespread RNA hypoediting in schizophrenia and its relevance to mitochondrial function},

author = {Mudra Choudhury and Ting Fu and Kofi Amoah and Hyun-Ik Jun and Tracey W Chan and Sungwoo Park and David W Walker and Jae Hoon Bahn and Xinshu Xiao},

doi = {10.1126/sciadv.ade9997},

issn = {2375-2548},

year  = {2023},

date = {2023-04-01},

journal = {Sci Adv},

volume = {9},

number = {14},

pages = {eade9997},

abstract = {RNA editing, the endogenous modification of nucleic acids, is known to be altered in genes with important neurological function in schizophrenia (SCZ). However, the global profile and molecular functions of disease-associated RNA editing remain unclear. Here, we analyzed RNA editing in postmortem brains of four SCZ cohorts and uncovered a significant and reproducible trend of hypoediting in patients of European descent. We report a set of SCZ-associated editing sites via WGCNA analysis, shared across cohorts. Using massively parallel reporter assays and bioinformatic analyses, we observed that differential 3' untranslated region (3'UTR) editing sites affecting host gene expression were enriched for mitochondrial processes. Furthermore, we characterized the impact of two recoding sites in the mitofusin 1 () gene and showed their functional relevance to mitochondrial fusion and cellular apoptosis. Our study reveals a global reduction of editing in SCZ and a compelling link between editing and mitochondrial function in the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37481717,

title = {Genetic pathways regulating the longitudinal acquisition of cocaine self-administration in a panel of inbred and recombinant inbred mice},

author = {Arshad H Khan and Jared R Bagley and Nathan LaPierre and Carlos Gonzalez-Figueroa and Tadeo C Spencer and Mudra Choudhury and Xinshu Xiao and Eleazar Eskin and James D Jentsch and Desmond J Smith},

doi = {10.1016/j.celrep.2023.112856},

issn = {2211-1247},

year  = {2023},

date = {2023-07-01},

journal = {Cell Rep},

volume = {42},

number = {8},

pages = {112856},

abstract = {To identify addiction genes, we evaluate intravenous self-administration of cocaine or saline in 84 inbred and recombinant inbred mouse strains over 10 days. We integrate the behavior data with brain RNA-seq data from 41 strains. The self-administration of cocaine and that of saline are genetically distinct. We maximize power to map loci for cocaine intake by using a linear mixed model to account for this longitudinal phenotype while correcting for population structure. A total of 15 unique significant loci are identified in the genome-wide association study. A transcriptome-wide association study highlights the Trpv2 ion channel as a key locus for cocaine self-administration as well as identifying 17 additional genes, including Arhgef26, Slc18b1, and Slco5a1. We find numerous instances where alternate splice site selection or RNA editing altered transcript abundance. Our work emphasizes the importance of Trpv2, an ionotropic cannabinoid receptor, for the response to cocaine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37474948,

title = {L-GIREMI uncovers RNA editing sites in long-read RNA-seq},

author = {Zhiheng Liu and Giovanni Quinones-Valdez and Ting Fu and Elaine Huang and Mudra Choudhury and Fairlie Reese and Ali Mortazavi and Xinshu Xiao},

doi = {10.1186/s13059-023-03012-w},

issn = {1474-760X},

year  = {2023},

date = {2023-07-01},

journal = {Genome Biol},

volume = {24},

number = {1},

pages = {171},

abstract = {Although long-read RNA-seq is increasingly applied to characterize full-length transcripts it can also enable detection of nucleotide variants, such as genetic mutations or RNA editing sites, which is significantly under-explored. Here, we present an in-depth study to detect and analyze RNA editing sites in long-read RNA-seq. Our new method, L-GIREMI, effectively handles sequencing errors and read biases. Applied to PacBio RNA-seq data, L-GIREMI affords a high accuracy in RNA editing identification. Additionally, our analysis uncovered novel insights about RNA editing occurrences in single molecules and double-stranded RNA structures. L-GIREMI provides a valuable means to study nucleotide variants in long-read RNA-seq.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}