We study computational and experimental RNA biology.

@article{nokey,

title = {Massively parallel screen uncovers many rare 3′ UTR variants regulating mRNA abundance of cancer driver genes},

author = {Ting Fu and Kofi Amoah and Tracey W. Chan and Jae Hoon Bahn and Jae-Hyung Lee and Sari Terrazas and Rockie Chong and Sriram Kosuri and Xinshu Xiao},

url = {https://www.nature.com/articles/s41467-024-46795-7},

year  = {2024},

date = {2024-04-18},

urldate = {2024-04-18},

journal = {Nature Communications},

volume = {15},

number = {3335},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38702197,

title = {Navigating the landscape of epitranscriptomics and host immunity},

author = {Elaine Huang and Clara Frydman and Xinshu Xiao},

doi = {10.1101/gr.278412.123},

issn = {1549-5469},

year  = {2024},

date = {2024-05-01},

journal = {Genome Res},

volume = {34},

number = {4},

pages = {515--529},

abstract = {RNA modifications, also termed epitranscriptomic marks, encompass chemical alterations to individual nucleotides, including processes such as methylation and editing. These marks contribute to a wide range of biological processes, many of which are related to host immune system defense. The functions of immune-related RNA modifications can be categorized into three main groups: regulation of immunogenic RNAs, control of genes involved in innate immune response, and facilitation of adaptive immunity. Here, we provide an overview of recent research findings that elucidate the contributions of RNA modifications to each of these processes. We also discuss relevant methods for genome-wide identification of RNA modifications and their immunogenic substrates. Finally, we highlight recent advances in cancer immunotherapies that aim to reduce cancer cell viability by targeting the enzymes responsible for RNA modifications. Our presentation of these dynamic research avenues sets the stage for future investigations in this field.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38815579,

title = {hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing},

author = {Rong Zheng and Mikayla Dunlap and Georg O M Bobkov and Carlos Gonzalez-Figueroa and Khushali J Patel and Jingyi Lyu and Samuel E Harvey and Tracey W Chan and Giovanni Quinones-Valdez and Mudra Choudhury and Charlotte A Le Roux and Mason D Bartels and Amy Vuong and Ryan A Flynn and Howard Y Chang and Eric L Van Nostrand and Xinshu Xiao and Chonghui Cheng},

doi = {10.1016/j.molcel.2024.05.004},

issn = {1097-4164},

year  = {2024},

date = {2024-05-01},

journal = {Mol Cell},

abstract = {RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites. hnRNPM preferentially binds at intronic LINEs to repress pseudo splice site usage for cryptic splicing. Remarkably, cryptic exons can generate long dsRNAs through base-pairing of inverted ALU transposable elements interspersed among LINEs and consequently trigger an interferon response, a well-known antiviral defense mechanism. Significantly, hnRNPM-deficient tumors show upregulated interferon-associated pathways and elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity by repressing cryptic splicing and suggest that targeting hnRNPM in tumors may be used to trigger an inflammatory immune response, thereby boosting cancer surveillance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38925119,

title = {Splicing-specific transcriptome-wide association uncovers genetic mechanisms for schizophrenia},

author = {Jonatan L Hervoso and Kofi Amoah and Jack Dodson and Mudra Choudhury and Arjun Bhattacharya and Giovanni Quinones-Valdez and Bogdan Pasaniuc and Xinshu Xiao},

doi = {10.1016/j.ajhg.2024.06.001},

issn = {1537-6605},

year  = {2024},

date = {2024-06-01},

journal = {Am J Hum Genet},

abstract = {Recent studies have highlighted the essential role of RNA splicing, a key mechanism of alternative RNA processing, in establishing connections between genetic variations and disease. Genetic loci influencing RNA splicing variations show considerable influence on complex traits, possibly surpassing those affecting total gene expression. Dysregulated RNA splicing has emerged as a major potential contributor to neurological and psychiatric disorders, likely due to the exceptionally high prevalence of alternatively spliced genes in the human brain. Nevertheless, establishing direct associations between genetically altered splicing and complex traits has remained an enduring challenge. We introduce Spliced-Transcriptome-Wide Associations (SpliTWAS) to integrate alternative splicing information with genome-wide association studies to pinpoint genes linked to traits through exon splicing events. We applied SpliTWAS to two schizophrenia (SCZ) RNA-sequencing datasets, BrainGVEX and CommonMind, revealing 137 and 88 trait-associated exons (in 84 and 67 genes), respectively. Enriched biological functions in the associated gene sets converged on neuronal function and development, immune cell activation, and cellular transport, which are highly relevant to SCZ. SpliTWAS variants impacted RNA-binding protein binding sites, revealing potential disruption of RNA-protein interactions affecting splicing. We extended the probabilistic fine-mapping method FOCUS to the exon level, identifying 36 genes and 48 exons as putatively causal for SCZ. We highlight VPS45 and APOPT1, where splicing of specific exons was associated with disease risk, eluding detection by conventional gene expression analysis. Collectively, this study supports the substantial role of alternative splicing in shaping the genetic basis of SCZ, providing a valuable approach for future investigations in this area.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}